2′, 5′-oligoadenylate analogs

ABSTRACT

A 2-5A analog represented by the formula (1): 
                         
wherein m is 0 or 1; n is 0 to 2; R 1  represents an alkoxy group having from 1 to 6 carbon atoms which may be substituted, an unprotected mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, or an alkylthio group having from 1 to 4 carbon atoms which may be substituted; R 2 , R 3 , R 4 , R 5  and R 6  represent an unprotected hydroxyl group, a hydroxyl group protected by a nucleic acid synthesis protecting group, an alkoxy group having from 1 to 6 carbon atoms which may be substituted, an unprotected mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, or an alkylthio group having from 1 to 4 carbon atoms which may be substituted; R 7  represents an oxygen atom, or a —O(CH 2 CH 2 O)q- group, wherein q is 2 to 6; R 8  represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms which may be substituted, or a 5′-phosphorylated oligonucleotide analog which has one hydroxyl group removed from the 5′-phosphoric acid group; E 1 , E 2 , E 3  and E 4  represent a naturally occurring or modified nucleic acid unit, or a pharmacologically acceptable salt thereof.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part application of International application PCT/JP2003/014748 filed Nov. 19, 2003, the entire contents of which are hereby incorporated by reference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to analogs of 2′,5′-oligoadenylate (2-5A) that are stable and have superior activity (particularly antitumor activity).

2. Background Art

2-5A, which is known as a biological substance that has antiviral activity (Pharmacol. Ther. Vol. 78, No. 2, pp. 55-113, 1998), is a short-chain oligonucleotide composed of three or more adenosine units in which two adenosine 2′ and 5′ hydroxyl groups are linked with phosphate 2′,5′-phosphodiester bonds, and in which a triphosphate group is bonded to the 5′ end. When cells infected by a virus are subjected to extracellular interferon stimulation, 2-5A synthetase is induced in the presence of viral dsRNA, and 2-5A is produced from ATP. 2-5A is a substance that converts the inactive form of the RNA degrading enzyme, RNase L, into the active form within host cells. This activated RNase L inhibits viral growth in cells by degrading viral RNA. Moreover, when ovarian cancer cells Hey1B are transfected with 2-5A, sequence-specific cleavage of 18S rRNA is known to occur, that results in demonstration of antitumor activity as a result of apoptosis through release of cytochrome c and activation of caspase (J. Interferon Cytokine Res., 20, 1091-1100 (2000)). Thus, 2-5A is expected to act as a virus growth inhibitor, and, more specifically, as an antivirus drug or antitumor drug.

In an in vitro experiment, an oligonucleotide composed of three or more adenosine units having a monophosphate group on the 5′ end and linked with 2′-5′ phosphodiester bonds is known to activate RNase L (Pharmacol. Ther. Vol. 78, No. 2, pp. 55-113, 1998; J. Biol. Chem. Vol. 270, No. 11, pp. 5963-5978 (1995)). However, 2-5A itself is easily degraded to AMP and ATP by 2′-phosphodiesterase and nuclease. Moreover, the 5′-phosphate group or 5′-triphosphate group ends up being dephosphorylated by phosphatases in the living body and losing activity. Thus, in the case of using 2-5A as a virus growth inhibitor or antitumor drug, a 2-5A analog is desirable that has similar activity, but has high stability, making it more resistant to degradation and metabolism in the living body.

In order to overcome these shortcomings, various methods have been attempted as examples of modifying the phosphate groups. Examples of known methods include a method in which the non-bridging oxygen atom bonded to the phosphorus atom of the phosphodiester bond of the oligonucleotide is substituted with a sulfur atom (phosphorothioate modification), a method in which said oxygen atom is substituted with a methyl group, a method in which said oxygen atom is substituted with a boron atom, and a method in which the sugar portion or nucleobase portion of the oligonucleotide is chemically modified (Freier, S. M.; Altmann, K. H., Nucleic Acids Res., 25, 4429 (1997)). A known example of such a 2-5A analog is the adenosine tetramer which has undergone the phosphorothioate modification shown below (Carpten, J. et al. Nature Genetics, 30, 181 (2002)).

Moreover, analogs having a chemical structure like that shown below, in which the sugar portion of adenosine has been modified, are described in Japanese Patent Application (Kokai) No. Hei 10-195098 and Japanese Patent No. 3420984 as adenosine units of 2-5A analogs.

In the above formula, Y¹ and Y² represent a hydrogen atom or a protecting group for a hydroxy group, and A represents an alkylene group having from 1 to 3 carbon atoms.

In addition, a 2-5A molecule bonded by means of a linker with an antisense molecule in the form of an oligonucleotide having a sequence complementary to mRNA involved in diseases has been used as a 2-5A antisense oligonucleotide that inhibits the function of mRNA (S. A. Adah, et al., Current Medicinal Chemistry (2001), 8, 1189-1212). A highly stable 2-5A analog that is resistant to degradation and metabolism in the living body serves as a portion of a superior 2-5A antisense oligonucleotide, and is expected to be a useful drug. In particular, oligonucleotides containing a bridged nucleoside in which an oxygen atom at the 2′ position and a carbon atom at the 4′ position of the sugar portion are bonded with an alkylene group are known to be useful as antisense molecules (Japanese Patent Application (Kokai) No. Hei 10-304889, Japanese Patent Application (Kokai) No. 2000-297097).

SUMMARY OF THE INVENTION

The inventors of the present invention conducted extensive research over the course of many years on non-natural type 2-5A analogs that have antivirus activity, antitumor activity or superior antisense activity, are stable in the living body, and are associated with the occurrence of few adverse side effects. As a result, they were found to be useful as stable and superior antivirus drugs, antitumor drugs and antisense drugs, thereby leading to completion of the present invention.

The 2-5A analog of the present invention relates to a 2′,5′-oligoadenylate analog represented by the general formula (1):

[wherein m represents an integer of 0 or 1; n represents an integer of 0 to 2; R¹ represents an alkoxy group having from 1 to 6 carbon atoms which may be substituted, a mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, an alkylthio group having from 1 to 4 carbon atoms which may be substituted, an amino group, an amino group protected by a nucleic acid synthesis protecting group, an amino group substituted by alkyl group(s), having from 1 to 6 carbon atoms which may be substituted, an alkyl group having from 1 to 6 carbon atoms which may be substituted, an aryloxy group which may be substituted, or an arylthio group which may be substituted, or a group of formula: X₁—X₂—X₃—S—; R², R³, R⁴, R⁵ and R⁶ represent a hydroxyl group, a hydroxyl group protected by a nucleic acid synthesis protecting group, an alkoxy group having from 1 to 6 carbon atoms which may be substituted, a mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, an alkylthio group having from 1 to 4 carbon atoms which may be substituted, an amino group, an amino group protected by a nucleic acid synthesis protecting group, an amino group substituted by alkyl group(s) having from 1 to 6 carbon atoms which may be substituted, or an alkyl group having from 1 to 6 carbon atoms which may be substituted; R⁷ represents an oxygen atom, a sulfur atom, —NH—, a —O(CH₂CH₂O)q- group (q represents an integer of 2 to 6), an oxyalkyleneoxy group having from 1 to 6 carbon atoms, or a group of formula: X₁—X₂—X₃—S—; R⁸ represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms which may be substituted, an aralkyl group which may be substituted, an aryl group which may be substituted, or a 5′-phosphorylated oligonucleotide analog which has one hydroxyl group removed from the 5′-phosphoric acid group; E¹, E², E³ and E⁴ are the same or different and represent K¹, K², K³ or K⁴ (K¹, K², K³ and K⁴ represent

respectively, wherein, B represents a purin-9-yl group or a substituted purin-9-yl group having substituent(s) selected from the following Group α, A represents an alkylene group having from 1 to 4 carbon atoms, D represents an alkyl group having from 1 to 6 carbon atoms which may be substituted, or an alkenyl group having from 2 to 6 carbon atoms which may be substituted); X₁ represents an alkyl group having from 1 to 24 carbon atoms which may be substituted, or an aryl group which may be substituted, or an aralkyl group which may be substituted; X₂ represents a —C(═O)O—, OC(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)S—, —SC(═O)—, —OC(═O)NH—, —NHC(═O)O—, —NHC(═O)NH—, —OC(═S)—, or a —C(═S)O—, —NHC(═S)—, —C(═S)NH— group; and X₃ represents an alkylene group having from 1 to 6 carbon atoms which may be substituted] (provided that compounds in which m is 0, n is 1, R², R³, R⁴ and R⁶ are a hydroxyl group, R⁷ is an oxygen atom, and R⁸ is a 2-hydroxyethyl group, and the compound in which m is 1, n is 0, R¹, R³, R⁹ and R⁵ are a mercapto group, R² is a hydroxyl group, R⁸ is a hydrogen atom, and all of E¹, E², E³ and E⁴ are K¹ are excluded), or a pharmacologically acceptable salt thereof. (Group α)

a hydroxyl group,

a hydroxyl group protected by a nucleic acid synthesis protecting group,

an alkoxy group having from 1 to 6 carbon atoms which may be substituted,

a mercapto group,

a mercapto group protected by a nucleic acid synthesis protecting group,

an alkylthio group having from 1 to 4 carbon atoms which may be substituted,

an amino group,

an amino group protected by a nucleic acid synthesis protecting group,

an amino group substituted by alkyl group(s) having from 1 to 4 carbon atoms which may be substituted,

an alkyl group having from 1 to 6 carbon atoms which may be substituted, and

a halogen atom.

The above 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof is preferably

(1) a 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof, in which R¹ is an alkoxy group having from 1 to 4 carbon atoms which may be substituted, a mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, or an alkylthio group having from 1 to 4 carbon atoms which may be substituted, or a group of formula: X₁—X₂—X₃—S—; R², R³, R⁴, R⁵ and R⁶ represent a hydroxyl group, a hydroxyl group protected by a nucleic acid synthesis protecting group, an alkoxy group having from 1 to 4 carbon atoms which may be substituted, a mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, an alkylthio group having from 1 to 4 carbon atoms which may be substituted, or a group of formula: X₁—X₂—X₃—S—; X₁ is an alkyl group having from 10 to 24 carbon atoms which may be substituted; X₂ is a —C(═O)O—, —C(═O)NH—, —C(═O)S—, —NHC(═O)O—, or —C(═S)NH— group; and X₃ is an alkylene group having from 1 to 4 carbon atoms which may be substituted; (2) a 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof, in which R⁷ represents an oxygen atom, a —O(CH₂CH₂O)q- group (q represents an integer of 2 to 6), or an oxyalkyleneoxy group having from 1 to 6 carbon atoms; and R⁸ is a hydrogen atom; an alkyl group having from 1 to 6 carbon atoms which may be substituted, or a 5′-phosphorylated oligonucleotide analog which has one hydroxyl group removed from the 5′-phosphoric acid group; (3) a 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof, wherein E² is K¹; (4) a 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof, wherein E¹ is K², and D is a methyl group or a 2-propenyl group; (5) a 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof, wherein E³ is K³ or K⁴, and A is a methylene, ethylene, or propylene group; (6) a 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof, wherein B is a 6-aminopurin-9-yl (that is, adeninyl), 6-amino-8-bromopurin-9-yl, 6-amino-8-chloropurin-9-yl, 6-amino-8-fluoropurin-9-yl, 6-amino-8-methoxypurin-9-yl, 6-amino-8-ethoxypurin-9-yl, 6-amino-8-t-butoxypurin-9-yl, 6-amino-2-bromopurin-9-yl, 6-amino-2-chloropurin-9-yl, 6-amino-2-fluoropurin-9-yl, 6-amino-2-methoxypurin-9-yl, 6-amino-2-ethoxypurin-9-yl, 6-amino-2-t-butoxypurin-9-yl, or 2,6-diaminopurin-9-yl group; or (7) a 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof, wherein B is 6-aminopurin-9-yl (that is, adeninyl) or 6-amino-8-bromopurin-9-yl.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a graph showing the cytotoxic activity on A549 cells as a result of the addition of compounds, namely, natural type 2-5A, the compound of Example 1 (Exemplary Compound No. 4), the compound of Example 2 (Exemplary Compound No. 1), the compound of Example 3 (Exemplary Compound No. 5) and the compound of Example 4 (Exemplary Compound No. 8).

DETAILED DESCRIPTION OF THE INVENTION

In the above general formula, the “alkylene group having from 1 to 4 carbon atoms” of A can be, for example, a methylene, ethylene, trimethylene or tetramethylene group, and is preferably an ethylene or trimethylene group.

In the above general formula (1), the protecting group of the “hydroxyl group protected by a nucleic acid synthesis protecting group” of R², R³, R⁴, R⁵ and R⁶ or the Group α is not particularly limited so long as it can stably protect a hydroxyl group during nucleic acid synthesis, and specifically means a protecting group stable under acidic or neutral conditions, and cleavable by a chemical method such as hydrogenolysis, hydrolysis, electrolysis or photolysis. Such a protecting group can be, for example, an “aliphatic acyl group” such as an alkylcarbonyl group, e.g., formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, nonanoyl, decanoyl, 3-methylnonanoyl, 8-methylnonanoyl, 3-ethyloctanoyl, 3,7-dimethyloctanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, 1-methylpentadecanoyl, 14-methylpentadecanoyl, 13,13-dimethyltetradecanoyl, heptadecanoyl, 15-methylhexadecanoyl, octadecanoyl, 1-methylheptadecanoyl, nonadecanoyl, eicosanoyl and heneicosanoyl; a carboxylated alkylcarbonyl group, e.g., succinoyl, glutaroyl and adipoyl; a halogeno lower alkylcarbonyl group, e.g., chloroacetyl, dichloroacetyl, trichloroacetyl and trifluoroacetyl; a lower alkoxy lower alkylcarbonyl group, e.g., methoxyacetyl; or an unsaturated alkylcarbonyl group, e.g., (E)-2-methyl-2-butenoyl;

a “lower alkyl group” such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl and 2-ethylbutyl; a “lower alkenyl group” such as ethenyl, 1-propenyl, 2-propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 2-ethyl-2-propenyl, 1-butenyl, 2-butenyl, 1-methyl-2-butenyl, 1-methyl-1-butenyl, 3-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 1-pentenyl, 2-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl and 5-hexenyl; an “aromatic acyl group” such as an arylcarbonyl group, e.g., benzoyl, α-naphthoyl and β-naphthoyl; a halogeno arylcarbonyl group, e.g., 2-bromobenzoyl and 4-chlorobenzoyl; a lower alkylated arylcarbonyl group, e.g., 2,4,6-trimethylbenzoyl and 4-toluoyl; a lower alkoxylated arylcarbonyl group, e.g., 4-anisoyl; a carboxylated arylcarbonyl group, e.g., 2-carboxybenzoyl, 3-carboxybenzoyl and 4-carboxybenzoyl; a nitrated arylcarbonyl group, e.g., 4-nitrobenzoyl and 2-nitrobenzoyl; a lower alkoxycarbonylated arylcarbonyl group, e.g., 2-(methoxycarbonyl)benzoyl; or an arylated arylcarbonyl group, e.g., 4-phenylbenzoyl; a “tetrahydropyranyl or tetrahydrothiopyranyl group” such as tetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl and 4-methoxytetrahydrothiopyran-4-yl; a “tetrahydrofuranyl or tetrahydrothiofuranyl group” such as tetrahydrofuran-2-yl and tetrahydrothiofuran-2-yl; a “silyl group” such as a tri-lower alkylsilyl group, e.g., trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl and triisopropylsilyl; or a tri-lower alkylsilyl group substituted by 1 or 2 aryl groups, e.g., diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl and phenyldiisopropylsilyl; a “lower alkoxymethyl group” such as methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl and t-butoxymethyl; a “lower alkoxylated lower alkoxymethyl group” such as 2-methoxyethoxymethyl; a “halogeno lower alkoxymethyl” such as 2,2,2-trichloroethoxymethyl and bis(2-chloroethoxy)methyl; a “lower alkoxylated ethyl group” such as 1-ethoxyethyl and 1-(isopropoxy)ethyl; a “halogenated ethyl group” such as 2,2,2-trichloroethyl; a “methyl group substituted by from 1 to 3 aryl groups” such as benzyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl and 9-anthrylmethyl; a “methyl group substituted by from 1 to 3 aryl groups whose aryl ring is substituted by lower alkyl, lower alkoxy, halogen or cyano group(s)” such as 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 4,4′-dimethoxytriphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl and 4-cyanobenzyl; a “lower alkoxycarbonyl group” such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl and isobutoxycarbonyl; an “aryl group substituted by halogen atom(s), lower alkoxy group(s) or nitro group(s)” such as 4-chlorophenyl, 2-chlorophenyl, 4-methoxyphenyl, 4-nitrophenyl and 2,4-dinitrophenyl; a “lower alkoxycarbonyl group substituted by halogen or tri-lower alkylsilyl group(s)” such as 2,2,2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl; an “alkenyloxycarbonyl group” such as vinyloxycarbonyl and allyloxycarbonyl; an “aralkyloxycarbonyl group whose aryl ring may be substituted by 1 or 2 lower alkoxy or nitro groups” such as benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl and 4-nitrobenzyloxycarbonyl; an “aliphatic acyloxymethyl group” such as an alkylcarbonyloxymethyl group, e.g., acetyloxymethyl, propionyloxymethyl, butyryloxymethyl, isobutyryloxymethyl, pentanoyloxymethyl, pivaloyloxymethyl, valeryloxymethyl, isovaleryloxymethyl, octanoyloxymethyl, nonanoyloxymethyl, decanoyloxymethyl, 3-methylnonanoyloxymethyl, 8-methylnonanoyloxymethyl, 3-ethyloctanoyloxymethyl, 3,7-dimethyloctanoyloxymethyl, undecanoyloxymethyl, dodecanoyloxymethyl, tridecanoyloxymethyl, tetradecanoyloxymethyl, pentadecanoyloxymethyl, hexadecanoyloxymethyl, 1-methylpentadecanoyloxymethyl, 14-methylpentadecanoyloxymethyl, 13,13-dimethyltetradecanoyloxymethyl, heptadecanoyloxymethyl, 15-methylhexadecanoyloxymethyl, octadecanoyloxymethyl, 1-methylheptadecanoyloxymethyl, nonadecanoyloxymethyl, eicosanoyloxymethyl and heneicosanoyloxymethyl; a carboxylated alkylcarbonyloxymethyl group, e.g., succinoyloxymethyl, glutaroyloxymethyl and adipoyloxymethyl; a halogeno lower alkylcarbonyloxymethyl group, e.g., chloroacetyloxymethyl, dichloroacetyloxymethyl, trichloroacetyloxymethyl and trifluoroacetyloxymethyl; a lower alkoxy lower alkylcarbonyloxymethyl group, e.g., methoxyacetyloxymethyl; or an unsaturated alkylcarbonyloxymethyl group, e.g., (E)-2-methyl-2-butenoyl; an “aliphatic acylthioethyl group” such as an alkylcarbonylthioethyl group, e.g., acetylthioethyl, propionylthioethyl, butyrylthioethyl, isobutyrylthioethyl, pentanoylthioethyl, pivaloylthioethyl, valerylthioethyl, isovalerylthioethyl, octanoylthioethyl, nonanoylthioethyl, decanoylthioethyl, 3-methylnonanoylthioethyl, 8-methylnonanoylthioethyl, 3-ethyloctanoylthioethyl, 3,7-dimethyloctanoylthioethyl, undecanoylthioethyl, dodecanoylthioethyl, tridecanoylthioethyl, tetradecanoylthioethyl, pentadecanoylthioethyl, hexadecanoylthioethyl, 1-methylpentadecanoylthioethyl, 14-methylpentadecanoylthioethyl, 13,13-dimethyltetradecanoylthioethyl, heptadecanoylthioethyl, 15-methylhexadecanoylthioethyl, octadecanoylthioethyl, 1-methylheptadecanoylthioethyl, nonadecanoylthioethyl, eicosanoylthioethyl and heneicosanoylthioethyl; a carboxylated alkylcarbonylthioethyl group, e.g., succinoylthioethyl, glutaroylthioethyl and adipoylthioethyl; a halogeno lower alkylcarbonylthioethyl group, e.g., chloroacetylthioethyl, dichloroacetylthioethyl, trichloroacetylthioethyl and trifluoroacetylthioethyl; a lower alkoxy lower alkylcarbonylthioethyl group, e.g., methoxyacetylthioethyl; or an unsaturated alkylcarbonylthioethyl group, e.g., (E)-2-methyl-2-butenoyl.

The protecting group of the “hydroxyl group protected by a nucleic acid synthesis protecting group” of R², R³, R⁴, R⁵ and R⁶ or the Group α is preferably a “methyl group substituted by from 1 to 3 aryl groups”, an “aryl group substituted by halogen atom(s), lower alkoxy group(s) or nitro group(s)”, a “lower alkyl group”, a “lower alkenyl group”, an “aliphatic acyloxymethyl group”, or an “aliphatic acylthioethyl group”, more preferably a benzyl group, a 2-chlorophenyl group, a 4-chlorophenyl group, a 2-propenyl group, a pivaloyloxymethyl group, an acetylthioethyl group, or a pivaloylthioethyl group.

In the above general formula (1), the “alkoxy group having from 1 to 6 carbon atoms which may be substituted” of R¹, R², R³, R⁴, R⁵, R⁶ or the Group α can be, for example, a “lower alkyloxy group” such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, n-pentyloxy, isopentyloxy, 2-methylbutoxy, neopentyloxy, 1-ethylpropoxy, n-hexyloxy, isohexyloxy, 4-methylpentyloxy, 3-methylpentyloxy, 2-methylpentyloxy, 1-methylpentyloxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,3-dimethylbutoxy and 2-ethylbutoxy;

a “lower alkyloxy group substituted by hydroxyl group(s)” such as 1-hydroxymethyloxy, 2-hydroxyethyloxy, 3-hydroxypropyloxy, 4-hydroxybutyloxy, 2-hydroxypropyloxy, 1-methyl-2-hydroxyethyloxy, 1-methyl-1-hydroxyethyloxy, 1,1-dimethyl-2-hydroxyethyloxy, 2-hydroxybutyloxy, 3-hydroxybutyloxy, 1-methyl-3-hydroxypropyloxy and 2-methyl-3-hydroxypropyloxy; a “lower alkyloxy group substituted by amino group(s)” such as 1-aminomethyloxy, 2-aminoethyloxy, 3-aminopropyloxy, 4-aminobutyloxy, 2-aminopropyloxy, 1-methyl-2-aminoethyloxy, 1-methyl-1-aminoethyloxy, 1,1-dimethyl-1-aminoethyloxy, 2-aminobutyloxy, 3-aminobutyloxy, 1-methyl-3-aminopropyloxy and 2-methyl-3-aminopropyloxy; a “lower alkyloxy group substituted by alkoxy group(s)” such as 1-methoxymethyloxy, 2-methoxyethyloxy, 3-methoxypropyloxy, 4-methoxybutyloxy, 2-methoxypropyloxy, 1-methyl-2-methoxyethyloxy, 1-methyl-1-methoxyethyloxy, 1,1-dimethyl-2-methoxyethyloxy, 2-methoxybutyloxy, 3-methoxybutyloxy, 1-methyl-3-methoxypropyloxy, 2-methyl-3-methoxypropyloxy, 1-ethoxymethyloxy, 2-ethoxyethyloxy, 3-ethoxypropyloxy, 4-ethoxybutyloxy, 2-ethoxypropyloxy, 1-methyl-2-ethoxyethyloxy, 1-methyl-1-ethoxyethyloxy, 1,1-dimethyl-2-ethoxyethyloxy, 2-ethoxybutyloxy, 3-ethoxybutyloxy, 1-methyl-3-ethoxypropyloxy and 2-methyl-3-ethoxypropyloxy; or a “cycloalkyloxy group” such as cyclopropoxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, norbornyloxy and adamantyloxy; and is preferably a 2-hydroxyethoxy group.

In the above general formula (1), the “oxyalkyleneoxy group having from 1 to 6 carbon atoms” of R⁷ can be, for example, an oxymethyleneoxy, oxyethyleneoxy, oxytrimethyleneoxy, oxytetramethyleneoxy, oxypentamethyleneoxy, or oxyhexamethyleneoxy group, and is preferably an oxytetramethyleneoxy or oxypentamethyleneoxy group.

In the above general formula (1), the protecting group of the “mercapto group protected by a nucleic acid synthesis protecting group” of R¹, R², R³, R⁴, R⁵ and R⁶ or the Group α is not particularly limited so long as it can stably protect a mercapto group during nucleic acid synthesis, and specifically means a protecting group stable under acidic or neutral conditions, and cleavable by a chemical method such as hydrogenolysis, hydrolysis, electrolysis or photolysis. Such a protecting group can be, for example, a “group which can form a disulfide” such as an alkylthio group, e.g., methylthio, ethylthio and tert-butylthio, or an arylthio group, e.g. benzylthio, in addition to the groups listed as a protecting group of a hydroxyl group, and is preferably an “aliphatic acyl group”, an “aromatic acyl group”, an “aliphatic acyloxymethyl group”, or an “aliphatic acylthioethyl group”, more preferably a pivaloyloxymethyl group, an acetylthioethyl group, or a pivaloylthioethyl group.

In the above general formula (1), the “alkylthio group having from 1 to 4 carbon atoms which may be substituted” of R¹, R², R³, R⁴, R⁵ and R⁶ or the Group α can be, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, s-butylthio, or tert-butylthio, and is preferably a methylthio or ethylthio group.

In the above general formula (1), the protecting group of the “amino group protected by a nucleic acid synthesis protecting group” of R¹ R², R³, R⁴, R⁵ and R⁶ or the Group α is not particularly limited so long as it can stably protect an amino group during nucleic acid synthesis, and specifically means a protecting group stable under acidic or neutral conditions and cleavable by a chemical method such as hydrogenolysis, hydrolysis, electrolysis or photolysis. Such a protecting group can be, for example, an “aliphatic acyl group” such as an alkylcarbonyl group, e.g., formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, nonanoyl, decanoyl, 3-methylnonanoyl, 8-methylnonanoyl, 3-ethyloctanoyl, 3,7-dimethyloctanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, 1-methylpentadecanoyl, 14-methylpentadecanoyl, 13,13-dimethyltetradecanoyl, heptadecanoyl, 15-methylhexadecanoyl, octadecanoyl, 1-methylheptadecanoyl, nonadecanoyl, eicosanoyl and heneicosanoyl; a carboxylated alkylcarbonyl group, e.g., succinoyl, glutaroyl and adipoyl; a halogeno lower alkylcarbonyl group, e.g., chloroacetyl, dichloroacetyl, trichloroacetyl and trifluoroacetyl; a lower alkoxy lower alkylcarbonyl group, e.g., methoxyacetyl; or an unsaturated alkylcarbonyl group, e.g., (E)-2-methyl-2-butenoyl;

an “aromatic acyl group” such as an arylcarbonyl group, e.g., benzoyl, α-naphthoyl and β-naphthoyl; a halogeno arylcarbonyl group, e.g., 2-bromobenzoyl and 4-chlorobenzoyl; a lower alkylated arylcarbonyl group, e.g., 2,4,6-trimethylbenzoyl and 4-toluoyl; a lower alkoxylated arylcarbonyl group, e.g., 4-anisoyl; a carboxylated arylcarbonyl group, e.g., 2-carboxybenzoyl, 3-carboxybenzoyl and 4-carboxybenzoyl; a nitrated arylcarbonyl group, e.g., 4-nitrobenzoyl and 2-nitrobenzoyl; a lower alkoxycarbonylated arylcarbonyl group, e.g., 2-(methoxycarbonyl)benzoyl; or an arylated arylcarbonyl group, e.g., 4-phenylbenzoyl;

a “lower alkoxycarbonyl group” such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl and isobutoxycarbonyl;

a “lower alkoxycarbonyl group substituted by halogen or tri-lower alkylsilyl group(s)” such as 2,2,2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl;

an “alkenyloxycarbonyl group” such as vinyloxycarbonyl and allyloxycarbonyl; or

an “aralkyloxycarbonyl group whose aryl ring may be substituted by 1 or 2 lower alkoxy or nitro groups” such as benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl and 4-nitrobenzyloxycarbonyl; and is preferably an “aliphatic acyl group” or an “aromatic acyl group”, more preferably a benzoyl group.

In the above general formula (1), the “amino group substituted by alkyl group(s) having from 1 to 4 carbon atoms which may be substituted” of R¹, R², R³, R⁴, R⁵ and R⁶ or the Group α can be, for example, a “lower alkylamino group” such as methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, s-butylamino, tert-butylamino, dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, diisobutylamino, di(s-butyl)amino and di(tert-butyl)amino;

a “lower alkylamino group substituted by hydroxyl group(s), lower alkoxy group(s) or halogen atom(s)” such as 1-hydroxyethylamino, 2-hydroxyethylamino, 1-methoxyethylamino, 2-methoxyethylamino, 1-bromoethylamino, 2-methoxyethylamino, 1-chloroethylamino and 2-chloroethylamino; or a “lower alkoxycarbonylamino group” such as 1-methoxycarbonylethylamino, 2-methoxycarbonylethylamino, 1-ethoxycarbonylethylamino, 2-ethoxycarbonylethylamino, 1-propoxycarbonylethylamino and 1-propoxycarbonylethylamino; and is preferably a 1-hydroxyethylamino, 2-hydroxyethylamino, methylamino, ethylamino, dimethylamino, diethylamino, diisopropylamino, 1-methoxycarbonylethylamino or 1-ethoxycarbonylethylamino group.

In the above general formula (1), the “alkyl group having from 1 to 6 carbon atoms which may be substituted” of D, R¹, R², R³, R⁴, R⁵, R⁶, R⁸ or the Group α can be, for example, a “lower alkyl group” such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl and 2-ethylbutyl;

a “lower alkyl group substituted by hydroxyl group(s)” such as 1-hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 2-hydroxypropyl, 1-methyl-2-hydroxyethyl, 1-methyl-1-hydroxyethyl, 1,1-dimethyl-2-hydroxyethyl, 2-hydroxybutyl, 3-hydroxybutyl, 1-methyl-3-hydroxypropyl and 2-methyl-3-hydroxypropyl; a “lower alkyl group substituted by amino group(s)” such as 1-aminomethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 2-aminopropyl, 1-methyl-2-aminoethyl, 1-methyl-1-aminoethyl, 1,1-dimethyl-2-aminoethyl, 2-aminobutyl, 3-aminobutyl, 1-methyl-3-aminopropyl and 2-methyl-3-aminopropyl; a “lower alkyl group substituted by alkoxy group(s)” such as 1-methoxymethyl, 2-methoxyethyl, 3-methoxypropyl, 4-methoxybutyl, 2-methoxypropyl, 1-methyl-2-methoxyethyl, 1-methyl-1-methoxyethyl, 1,1-dimethyl-2-methoxyethyl, 2-methoxybutyl, 3-methoxybutyl, 1-methyl-3-methoxypropyl, 2-methyl-3-methoxypropyl, 1-ethoxymethyl, 2-ethoxyethyl, 3-ethoxypropyl, 4-ethoxybutyl, 2-ethoxypropyl, 1-methyl-2-ethoxyethyl, 1-methyl-1-ethoxyethyl, 1,1-dimethyl-2-ethoxyethyl, 2-ethoxybutyl, 3-ethoxybutyl, 1-methyl-3-ethoxypropyl and 2-methyl-3-ethoxypropyl; or a “cycloalkyl group” such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl and adamantyl; and is preferably a 2-methoxyethyl group or a 2-hydroxyethyl group.

In the above general formula (1), the “alkyl group having from 1 to 24 carbon atoms which may be substituted” of X₁ can be, for example, stearyl, 2,2-dimethylstearyl, heptadecyl, 2,2-dimethylheptadecyl, hexadecyl, 2,2-dimethylhexadecyl, pentadecyl, 2,2-dimethylpentadecyl, tetradecyl, 2,2-dimethyltetradecyl, tridecyl, 2,2-dimethyltridecyl, dodecyl, 2,2-dimethyldodecyl, undecyl, 2,2-dimethylundecyl, decyl, 2,2-dimethyldecyl, nonyl, 2,2-dimethylnonyl, octyl, 2,2-dimethyloctyl, heptyl, 2,2-dimethylheptyl, hexyl, 2,2-dimethylhexyl, pentyl, 2,2-dimethylpentyl, butyl, 2,2-dimethylbutyl, propyl, 2,2-tert-butyl, ethyl, or methyl, and is preferably stearyl or 2,2-dimethylstearyl.

In the above general formula (1), the “alkylene group having from 1 to 6 carbon atoms which may be substituted” of X₃ can be, for example, methylene, ethylene, propylene, butylene, 2,2-dimethylethylene, 2,2-dimethylpropylene, or 2,2-dimethylbutylene, and is preferably methylene or ethylene.

In the above general formula (1), the “aryloxy group which may be substituted” of R¹ can be, for example, an “aryloxy group substituted by lower alkyl group(s), halogen atom(s) or nitro group(s)” such as 2-methylphenoxy, 3-methylphenoxy, 4-methylphenoxy, 2,6-dimethylphenoxy, 2-chlorophenoxy, 4-chlorophenoxy, 2,4-dichlorophenoxy, 2,5-dichlorophenoxy, 2-bromophenoxy, 4-nitrophenoxy and 4-chloro-2-nitrophenoxy.

In the above general formula (1), the “aryl group which may be substituted” of R⁸ or X₁ can be, for example, an “aryl group substituted by lower alkyl group(s), halogen atom(s) or nitro group(s)” such as 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,6-dimethylphenyl, 2-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2-bromophenyl, 4-nitrophenyl and 4-chloro-2-nitrophenyl.

In the above general formula (1), the “arylthio group which may be substituted” of R¹ can be, for example, an “arylthio group substituted by lower alkyl group(s), halogen atom(s) or nitro group(s)” such as 2-methylphenylthio, 3-methylphenylthio, 4-methylphenylthio, 2,6-dimethylphenylthio, 2-chlorophenylthio, 4-chlorophenylthio, 2,4-dichlorophenylthio, 2,5-dichlorophenylthio, 2-bromophenylthio, 4-nitrophenylthio and 4-chloro-2-nitrophenylthio.

In the above general formula (1), the “alkenyl group having from 2 to 6 carbon atoms which may be substituted” of D can be, for example, ethenyl, 1-propenyl, 2-propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 2-ethyl-2-propenyl, 1-butenyl, 2-butenyl, 1-methyl-2-butenyl, 1-methyl-1-butenyl, 3-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 1-pentenyl, 2-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, or 5-hexenyl.

In the above general formula (1), the “aralkyl group which may be substituted” of R⁸ or X₁ can be, for example, an “aralkyl group” such as benzyl, α-naphthylmethyl, β-naphthylmethyl, indenylmethyl, phenanthrenylmethyl, anthracenylmethyl, diphenylmethyl, triphenylmethyl, 1-phenethyl, 2-phenethyl, 1-naphthylethyl, 2-naphthylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 1-naphthylpropyl, 2-naphthylpropyl, 3-naphthylpropyl, 1-phenylbutyl, 2-phenylbutyl, 3-phenylbutyl, 4-phenylbutyl, 1-naphthylbutyl, 2-naphthylbutyl, 3-naphthylbutyl, 4-naphthylbutyl, 1-phenylpentyl, 2-phenylpentyl, 3-phenylpentyl, 4-phenylpentyl, 5-phenylpentyl, 1-naphthylpentyl, 2-naphthylpentyl, 3-naphthylpentyl, 4-naphthylpentyl, 5-naphthylpentyl, 1-phenylhexyl, 2-phenylhexyl, 3-phenylhexyl, 4-phenylhexyl, 5-phenylhexyl, 6-phenylhexyl, 1-naphthylhexyl, 2-naphthylhexyl, 3-naphthylhexyl, 4-naphthylhexyl, 5-naphthylhexyl and 6-naphthylhexyl; or an “aralkyl group whose aryl ring is substituted by nitro group(s) or halogen atom(s)” such as 4-chlorobenzyl, 2-(4-nitrophenyl)ethyl, o-nitrobenzyl, 4-nitrobenzyl, 2,4-dinitrobenzyl and 4-chloro-2-nitrobenzyl.

In the above general formula (1), of all of the “purin-9-yl group” and the “substituted purin-9-yl group” of B, the preferred groups are 6-amino-purin-9-yl (that is, adeninyl), 6-amino-purin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-8-bromopurin-9-yl, 6-amino-8-bromopurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-8-chloropurin-9-yl, 6-amino-8-chloropurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-8-fluoropurin-9-yl, 6-amino-8-fluoropurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-8-methoxypurin-9-yl, 6-amino-8-methoxypurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-8-ethoxypurin-9-yl, 6-amino-8-ethoxypurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-8-t-butoxypurin-9-yl, 6-amino-8-t-butoxypurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 2,6-diaminopurin-9-yl, 2-amino-6-chloropurin-9-yl, 2-amino-6-chloropurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 2-amino-6-fluoropurin-9-yl, 2-amino-6-fluoropurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 2-amino-6-bromopurin-9-yl, 2-amino-6-bromopurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 2-amino-6-hydroxypurin-9-yl (that is, guaninyl), 2-amino-6-hydroxypurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-2-methoxypurin-9-yl, 6-amino-2-methoxypurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-2-chloropurin-9-yl, 6-amino-2-chloropurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 6-amino-2-fluoropurin-9-yl, 6-amino-2-fluoropurin-9-yl in which the amino group is protected by a nucleic acid synthesis protecting group, 2,6-dimethoxypurin-9-yl, 2,6-dichloropurin-9-yl, and 6-mercaptopurin-9-yl group, and the more preferred groups are 6-benzoylaminopurin-9-yl or adeninyl.

There is no particular limitation on the functional group represented by “X₁—X₂—X₃—S”, provided that it is a combination comprising X₁, X₂, X₃ and S mentioned above, and it can be, for example, an acyloxyalkylthio group such as 2-(stearoyloxy)ethylthio, 2-(myristoyloxy)ethylthio, 2-(decanoyloxy)ethylthio, 2-(benzoyloxy)ethylthio, 2-(pivaloyloxy)ethylthio, 2-(2,2-dimethyloctadecanoyloxy)ethylthio, 3-(stearoyloxy)propylthio, 3-(myristoyloxy)propylthio, 3-(decanoyloxy)propylthio, 3-(benzoyloxy)propylthio, 3-(pivaloyloxy)propylthio, 3-(2,2-dimethyloctadecanoyloxy)propylthio, 4-(stearoyloxy)butylthio, 4-(myristoyloxy)butylthio, 4-(decanoyloxy)butylthio, 4-(benzoyloxy)butylthio, 4-(pivaloyloxy)butylthio and 4-(2,2-dimethyloctadecanoyloxy)butylthio, or an alkylcarbamoyloxyalkylthio group such as 2-(stearylcarbamoyloxy)ethylthio, or the following compounds:

and is preferably a 2-stearoyloxyethylthio or 2-(2,2-dimethyloctadecanoyloxy)ethylthio group.

In the above general formula (1), the “halogen atom” of the Group α can be, for example, a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and is preferably a bromine atom or a chlorine atom.

The “2′,5′-oligoadenylate analog (2-5A analog)” means a non-natural type derivative of “2′,5′-oligoadenylate”, in which the 2′ position and 5′ position of the 3 or 4 “nucleosides”, being the same or different, are bonded by a phosphodiester bond linkage or a modified phosphodiester linkage, and a phosphoryl derivative is bonded to the 5′-terminal, or a phosphoryl derivative is optionally bonded to the 2′-terminal, or a 5′-phosphorylated oligonucleotide analog is optionally bonded to the 2′-terminal through an alkylene linker. Such an analog can preferably be a sugar derivative wherein the sugar portion is modified; a thioate derivative wherein the phosphodiester bonding portion is thioated; a phosphoryl derivative wherein the phosphoric acid portion at the terminal is substituted; or a purine derivative wherein the purine base is substituted; and is more preferably a phosphoryl derivative wherein the phosphoric acid portion at the terminal is substituted, a sugar derivative wherein the sugar portion is modified, or a thioate derivative wherein the phosphodiester bonding portion is thioated.

The “5′-phosphorylated oligonucleotide analog which has one hydroxyl group removed from the 5′-phosphoric acid group” means a non-natural type derivative of “oligonucleotide” in which 2 to 50 “nucleosides” being the same or different, are bonded by phosphodiester bond linkages, and means a derivative having the following residual group:

(wherein R⁶ has the same meaning as defined above) instead of the hydroxyl group at the 5′ end of the oligonucleotide.

Such an analog can preferably be a sugar derivative wherein the sugar portion is modified; a thioate derivative wherein the phosphodiester bonding portion is thioated; an ester wherein the phosphoric acid portion at the terminal is esterified; or an amide wherein the amino group on the purine base is amidated; and is more preferably a sugar derivative wherein the sugar portion is modified, or a thioate derivative wherein the phosphodiester bonding portion is thioated.

“Salt thereof” means a salt of the compound (1) of the present invention, since the compound can be converted to a salt. Such a salt can preferably be a metal salt such as an alkali metal salt, e.g., a sodium salt, a potassium salt and a lithium salt; an alkaline earth metal salt, e.g., a calcium salt and a magnesium salt; an aluminum salt, an iron salt, a zinc salt, a copper salt, a nickel salt or a cobalt salt; an amine salt such as inorganic salt, e.g., an ammonium salt; or an organic salt, e.g., a t-octylamine salt, a dibenzylamine salt, a morpholine salt, a glucosamine salt, a phenylglycine alkyl ester salt, an ethylenediamine salt, an N-methylglucamine salt, a guanidine salt, a diethylamine salt, a triethylamine salt, a dicyclohexylamine salt, an N,N′-dibenzylethylenediamine salt, a chloroprocaine salt, a procaine salt, a diethanolamine salt, an N-benzylphenethylamine salt, a piperazine salt, a tetramethylammonium salt and a tris(hydroxymethyl)aminomethane salt; an inorganic acid salt such as a hydrogen halide salt, e.g., hydrofluoride, hydrochloride, hydrobromide and hydroiodide; nitrate, perchlorate, sulfate or phosphate; or an organic acid salt such as a lower alkanesulfonate, e.g., methanesulfonate, trifluoromethanesulfonate and ethanesulfonate; an arylsulfonate, e.g., benzenesulfonate and p-toluenesulfonate; acetate, malate, fumarate, succinate, citrate, tartrate, oxalate or maleate; or an amino acid salt such as a glycine salt, a lysine salt, an arginine salt, an ornithine salt, a glutamate, or an aspartate.

A “pharmacologically acceptable salt thereof” means a salt of the 2-5A analog of the present invention, since it can be converted into a salt. Such a salt can preferably be a metal salt such as an alkali metal salt, e.g., a sodium salt, a potassium salt and a lithium salt; an alkaline earth metal salt, e.g., a calcium salt and a magnesium salt; an aluminum salt, an iron salt, a zinc salt, a copper salt, a nickel salt or a cobalt salt; an amine salt such as an inorganic salt, e.g., an ammonium salt; or an organic salt; e.g., a t-octylamine salt, a dibenzylamine salt, a morpholine salt, a glucosamine salt, a phenylglycine alkyl ester salt, an ethylenediamine salt, an N-methylglucamine salt, a guanidine salt, a diethylamine salt, a triethylamine salt, a dicyclohexylamine salt, an N,N′-dibenzylethylenediamine salt, a chloroprocaine salt, a procaine salt, a diethanolamine salt, an N-benzylphenethylamine salt, a piperazine salt, a tetramethylammonium salt and a tris(hydroxymethyl)aminomethane salt; an inorganic acid salt such as a hydrogen halide salt, e.g., hydrofluoride, hydrochloride, hydrobromide and hydroiodide; nitrate, perchlorate, sulfate or phosphate; or an organic acid salt such as a lower alkanesulfonate, e.g., methanesulfonate, trifluoromethanesulfonate and ethanesulfonate; an arylsulfonate, e.g., benzenesulfonate and p-toluenesulfonate; acetate, malate, fumarate, succinate, citrate, tartrate, oxalate or maleate; or an amino acid salt such as a glycine salt, a lysine salt, an arginine salt, an ornithine salt, a glutamate, or an aspartate.

Specific compounds included in the compound of the above formula (1) of the present invention are illustrated in Table 1. However, the compounds of the present invention are not limited to these.

TABLE 1

Exemplified Compound No. E¹ E² E³ E⁴ R¹ R² R³ R⁴ R⁵ R⁶ R⁷ R⁸ m n 1 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH OH — — — H 0 0 2 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — — — H 0 0 3 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH OH — — — H 0 0 4 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — — — H 0 0 5 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — — — H 0 0 6 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH — — H 1 0 7 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH SH SH SH SH — — H 1 0 8 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — — — H 0 0 9 K²⁻² K¹⁻¹ K³⁻¹ — OH SH OH OH — — — H 0 0 10 K²⁻³ K¹⁻¹ K³⁻¹ — OH SH OH OH — — — H 0 0 11 K²⁻⁴ K¹⁻¹ K³⁻¹ — OH SH OH OH — — — H 0 0 12 K²⁻¹ K¹⁻² K³⁻¹ — OH SH OH OH — — — H 0 0 13 K²⁻¹ K¹⁻¹ K³⁻² — OH SH OH OH — — — H 0 0 14 K²⁻¹ K¹⁻¹ K³⁻³ — OH SH OH OH — — — H 0 0 15 K²⁻¹ K¹⁻¹ K³⁻⁴ — OH SH OH OH — — — H 0 0 16 K²⁻¹ K¹⁻¹ K³⁻⁵ — OH SH OH OH — — — H 0 0 17 K²⁻² K¹⁻² K³⁻² — OH SH OH OH — — — H 0 0 18 K²⁻² K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH OH — — — H 0 0 19 K²⁻³ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH OH — — — H 0 0 20 K²⁻⁴ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH OH — — — H 0 0 21 K²⁻¹ K¹⁻² K³⁻¹ — OC₂H₄OH SH OH OH — — — H 0 0 22 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH SH OH OH — — — H 0 0 23 K²⁻¹ K¹⁻¹ K³⁻³ — OC₂H₄OH SH OH OH — — — H 0 0 24 K²⁻¹ K¹⁻¹ K³⁻⁴ — OC₂H₄OH SH OH OH — — — H 0 0 25 K²⁻¹ K¹⁻¹ K³⁻⁵ — OC₂H₄OH SH OH OH — — — H 0 0 26 K²⁻² K¹⁻² K³⁻² — OC₂H₄OH SH OH OH — — — H 0 0 27 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH OH SH SH — — — H 0 0 28 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH SH SH SH — — — H 0 0 29 K¹⁻¹ K¹⁻¹ K¹⁻² K¹⁻¹ OC₂H₄OH OH SH SH SH — — H 1 0 30 K¹⁻¹ K¹⁻¹ K¹⁻² K¹⁻¹ OC₂H₄OH SH SH SH SH — — H 1 0 31 K¹⁻¹ K¹⁻¹ K¹⁻² — OH SH SH SH — — — H 0 0 32 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH OH — O(CH₂)₃OH O H 0 1 33 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — O(CH₂)₃OH O H 0 1 34 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH OH — O(CH₂)₃OH O H 0 1 35 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — O(CH₂)₃OH O H 0 1 36 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — O(CH₂)₃OH O H 0 1 37 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH O(CH₂)₃OH O H 1 1 38 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH OH OH — O(CH₂)₃OH O H 0 1 39 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — O(CH₂)₃OH O H 0 1 40 K¹⁻¹ K¹⁻¹ K³⁻² — OH SH OH OH — O(CH₂)₃OH O H 0 1 41 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH OH SH SH — O(CH₂)₃OH O H 0 1 42 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH SH SH SH — O(CH₂)₃OH O H 0 1 43 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH OH — O(CH₂)₄OH O H 0 1 44 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — O(CH₂)₄OH O H 0 1 45 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH OH — O(CH₂)₄OH O H 0 1 46 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — O(CH₂)₄OH O H 0 1 47 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — O(CH₂)₄OH O H 0 1 48 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH O(CH₂)₄OH O H 1 1 49 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH OH OH — O(CH₂)₄OH O H 0 1 50 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — O(CH₂)₄OH O H 0 1 51 K²⁻¹ K¹⁻¹ K³⁻² — OH SH OH OH — O(CH₂)₄OH O H 0 1 52 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH OH SH SH — O(CH₂)₄OH O H 0 1 53 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH SH 5H SH — O(CH₂)₄OH O H 0 1 54 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH OH — O(CH₂)₂OH O H 0 2 55 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — O(CH₂)₂OH O H 0 2 56 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH OH — O(CH₂)₂OH O H 0 2 57 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — O(CH₂)₂OH O H 0 2 58 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — O(CH₂)₂OH O H 0 2 59 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH O(CH₂)₂OH O H 1 2 60 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH OH OH — O(CH₂)₂OH O H 0 2 61 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — O(CH₂)₂OH O H 0 2 62 K¹⁻¹ K¹⁻¹ K³⁻² — OH SH OH OH — O(CH₂)₂OH O H 0 2 63 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH OH SH SH — O(CH₂)₂OH O H 0 2 64 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH SH SH SH — O(CH₂)₂OH O H 0 2 65 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH OH OH — — — H 0 0 66 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH OH OH — — — H 0 0 67 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₆OH OH OH OH — — — H 0 0 68 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₈OH OH OH OH — — — H 0 0 69 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃NH₂ OH OH OH — — — H 0 0 70 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₆NH₂ OH OH OH — — — H 0 0 71 K²⁻¹ K¹⁻¹ K³⁻¹ — OPh OH OH OH — — — H 0 0 72 K²⁻¹ K¹⁻¹ K³⁻¹ — OBn OH OH OH — — — H 0 0 73 K²⁻¹ K¹⁻¹ K³⁻¹ — OMe OH OH OH — — — H 0 0 74 K²⁻¹ K¹⁻¹ K³⁻¹ — OEt OH OH OH — — — H 0 0 75 K²⁻¹ K¹⁻¹ K³⁻¹ — OPr OH OH OH — — — H 0 0 76 K²⁻¹ K¹⁻¹ K³⁻¹ — Gly OH OH OH — — — H 0 0 77 K²⁻¹ K¹⁻¹ K³⁻¹ — Me OH OH OH — — — H 0 0 78 K²⁻¹ K¹⁻¹ K³⁻¹ — Et OH OH OH — — — H 0 0 79 K²⁻¹ K¹⁻¹ K³⁻¹ — CH₂OH OH OH OH — — — H 0 0 80 K²⁻¹ K¹⁻¹ K³⁻¹ — C₂H₄OH OH OH OH — — — H 0 0 81 K²⁻¹ K¹⁻¹ K³⁻¹ — Ph OH OH OH — — — H 0 0 82 K²⁻¹ K¹⁻¹ K³⁻¹ — CH₂Ph OH OH OH — — — H 0 0 83 K²⁻¹ K¹⁻¹ K³⁻¹ — NH₂ OH OH OH — — — H 0 0 84 K²⁻¹ K¹⁻¹ K³⁻¹ — NHPh OH OH OH — — — H 0 0 85 K²⁻¹ K¹⁻¹ K³⁻¹ — N(Me)₂ OH OH OH — — — H 0 0 86 K²⁻¹ K¹⁻¹ K³⁻¹ — N(Et)₂ OH OH OH — — — H 0 0 87 K²⁻¹ K¹⁻¹ K³⁻¹ — SMe OH OH OH — — — H 0 0 88 K²⁻¹ K¹⁻¹ K³⁻¹ — SEt OH OH OH — — — H 0 0 89 K²⁻¹ K¹⁻¹ K³⁻¹ — SPh OH OH OH — — — H 0 0 90 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH SH OH OH — — — H 0 0 91 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH SH OH OH — — — H 0 0 92 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₆OH SH OH OH — — — H 0 0 93 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₈OH SH OH OH — — — H 0 0 94 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃NH₂ SH OH OH — — — H 0 0 95 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₆NH₂ SH OH OH — — — H 0 0 96 K²⁻¹ K¹⁻¹ K³⁻¹ — OPh SH OH OH — — — H 0 0 97 K²⁻¹ K¹⁻¹ K³⁻¹ — OBn SH OH OH — — — H 0 0 98 K²⁻¹ K¹⁻¹ K³⁻¹ — OMe SH OH OH — — — H 0 0 99 K²⁻¹ K¹⁻¹ K³⁻¹ — OEt SH OH OH — — — H 0 0 100 K²⁻¹ K¹⁻¹ K³⁻¹ — OPr SH OH OH — — — H 0 0 101 K²⁻¹ K¹⁻¹ K³⁻¹ — Gly SH OH OH — — — H 0 0 102 K²⁻¹ K¹⁻¹ K³⁻¹ — Me SH OH OH — — — H 0 0 103 K²⁻¹ K¹⁻¹ K³⁻¹ — Et SH OH OH — — — H 0 0 104 K²⁻¹ K¹⁻¹ K³⁻¹ — CH₂OH SH OH OH — — — H 0 0 105 K²⁻¹ K¹⁻¹ K³⁻¹ — C₂H₄OH SH OH OH — — — H 0 0 106 K²⁻¹ K¹⁻¹ K³⁻¹ — Ph SH OH OH — — — H 0 0 107 K²⁻¹ K¹⁻¹ K³⁻¹ — CH₂Ph SH OH OH — — — H 0 0 108 K²⁻¹ K¹⁻¹ K³⁻¹ — NH₂ SH OH OH — — — H 0 0 109 K²⁻¹ K¹⁻¹ K³⁻¹ — NHPh SH OH OH — — — H 0 0 110 K²⁻¹ K¹⁻¹ K³⁻¹ — N(Me)₂ SH OH OH — — — H 0 0 111 K²⁻¹ K¹⁻¹ K³⁻¹ — N(Et)₂ SH OH OH — — — H 0 0 112 K²⁻¹ K¹⁻¹ K³⁻¹ — SMe SH OH OH — — — H 0 0 113 K²⁻¹ K¹⁻¹ K³⁻¹ — SEt SH OH OH — — — H 0 0 114 K²⁻¹ K¹⁻¹ K³⁻¹ — SPh SH OH OH — — — H 0 0 115 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH NH₂ OH OH — — — H 0 0 116 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH NH₂ OH OH — — — H 0 0 117 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₆OH NH₂ OH OH — — — H 0 0 118 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₈OH NH₂ OH OH — — — H 0 0 119 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃NH₂ NH₂ OH OH — — — H 0 0 120 K²⁻¹ K¹⁻¹ K³⁻¹ — O(OH₂)₆NH₂ NH₂ OH OH — — — H 0 0 121 K²⁻¹ K¹⁻¹ K³⁻¹ — OPh NH₂ OH OH — — — H 0 0 122 K²⁻¹ K¹⁻¹ K³⁻¹ — OBn NH₂ OH OH — — — H 0 0 123 K²⁻¹ K¹⁻¹ K³⁻¹ — OMe NH₂ OH OH — — — H 0 0 124 K²⁻¹ K¹⁻¹ K³⁻¹ — OEt NH₂ OH OH — — — H 0 0 125 K²⁻¹ K¹⁻¹ K³⁻¹ — OPr NH₂ OH OH — — — H 0 0 126 K²⁻¹ K¹⁻¹ K³⁻¹ — Gly NH₂ OH OH — — — H 0 0 127 K²⁻¹ K¹⁻¹ K³⁻¹ — Me NH₂ OH OH — — — H 0 0 128 K²⁻¹ K¹⁻¹ K³⁻¹ — Et NH₂ OH OH — — — H 0 0 129 K²⁻¹ K¹⁻¹ K³⁻¹ — CH₂OH NH₂ OH OH — — — H 0 0 130 K²⁻¹ K¹⁻¹ K³⁻¹ — C₂H₄OH NH₂ OH OH — — — H 0 0 131 K²⁻¹ K¹⁻¹ K³⁻¹ — Ph NH₂ OH OH — — — H 0 0 132 K²⁻¹ K¹⁻¹ K³⁻¹ — CH₂Ph NH₂ OH OH — — — H 0 0 133 K²⁻¹ K¹⁻¹ K³⁻¹ — NH₂ NH₂ OH OH — — — H 0 0 134 K²⁻¹ K¹⁻¹ K³⁻¹ — NHPh NH₂ OH OH — — — H 0 0 135 K²⁻¹ K¹⁻¹ K³⁻¹ — N(Me)₂ NH₂ OH OH — — — H 0 0 136 K²⁻¹ K¹⁻¹ K³⁻¹ — N(Et)₂ NH₂ OH OH — — — H 0 0 137 K²⁻¹ K¹⁻¹ K³⁻¹ — SMe NH₂ OH OH — — — H 0 0 138 K²⁻¹ K¹⁻¹ K³⁻¹ — SEt NH₂ OH OH — — — H 0 0 139 K²⁻¹ K¹⁻¹ K³⁻¹ — SPh NH₂ OH OH — — — H 0 0 140 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₂OH OH SH SH — — — H 0 0 141 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH OH SH SH — — — H 0 0 142 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₆OH OH SH SH — — — H 0 0 143 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₈OH OH SH SH — — — H 0 0 144 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃NH₂ OH SH SH — — — H 0 0 145 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₆NH₂ OH SH SH — — — H 0 0 146 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPh OH SH SH — — — H 0 0 147 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OBn OH SH SH — — — H 0 0 148 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OMe OH SH SH — — — H 0 0 149 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OEt OH SH SH — — — H 0 0 150 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPr OH SH SH — — — H 0 0 151 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Gly OH SH SH — — — H 0 0 152 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Me OH SH SH — — — H 0 0 153 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Et OH SH SH — — — H 0 0 154 K¹⁻¹ K¹⁻¹ K¹⁻¹ — CH₂OH OH SH SH — — — H 0 0 155 K¹⁻¹ K¹⁻¹ K¹⁻¹ — C₂H₄OH OH SH SH — — — H 0 0 156 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Ph OH SH SH — — — H 0 0 157 K¹⁻¹ K¹⁻¹ K¹⁻¹ — CH₂Ph OH SH SH — — — H 0 0 158 K¹⁻¹ K¹⁻¹ K¹⁻¹ — NH₂ OH SH SH — — — H 0 0 159 K¹⁻¹ K¹⁻¹ K¹⁻¹ — NHPh OH SH SH — — — H 0 0 160 K¹⁻¹ K¹⁻¹ K¹⁻¹ — N(Me)₂ OH SH SH — — — H 0 0 161 K¹⁻¹ K¹⁻¹ K¹⁻¹ — N(Et)₂ OH SH SH — — — H 0 0 162 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SMe OH SH SH — — — H 0 0 163 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SEt OH SH SH — — — H 0 0 164 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SPh OH SH SH — — — H 0 0 165 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃OH SH SH SH — — — H 0 0 166 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH SH SH SH — — — H 0 0 167 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₆OH SH SH SH — — — H 0 0 168 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₈OH SH SH SH — — — H 0 0 169 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃NH₂ SH SH SH — — — H 0 0 170 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₆NH₂ SH SH SH — — — H 0 0 171 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPh SH SH SH — — — H 0 0 172 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OBn SH SH SH — — — H 0 0 173 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OMe SH SH SH — — — H 0 0 174 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OEt SH SH SH — — — H 0 0 175 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPr SH SH SH — — — H 0 0 176 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Gly SH SH SH — — — H 0 0 177 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Me SH SH SH — — — H 0 0 178 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Et SH SH SH — — — H 0 0 179 K¹⁻¹ K¹⁻¹ K¹⁻¹ — CH₂OH SH SH SH — — — H 0 0 180 K¹⁻¹ K¹⁻¹ K¹⁻¹ — C₂H₄OH SH SH SH — — — H 0 0 181 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Ph SH SH SH — — — H 0 0 182 K¹⁻¹ K¹⁻¹ K¹⁻¹ — CH₂Ph SH SH SH — — — H 0 0 183 K¹⁻¹ K¹⁻¹ K¹⁻¹ — NH₂ SH SH SH — — — H 0 0 184 K¹⁻¹ K¹⁻¹ K¹⁻¹ — NHPh SH SH SH — — — H 0 0 185 K¹⁻¹ K¹⁻¹ K¹⁻¹ — N(Me)₂ SH SH SH — — — H 0 0 186 K¹⁻¹ K¹⁻¹ K¹⁻¹ — N(Et)₂ SH SH SH — — — H 0 0 187 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SMe SH SH SH — — — H 0 0 188 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SEt SH SH SH — — — H 0 0 189 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SPh SH SH SH — — — H 0 0 190 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃OH NH₂ SH SH — — — H 0 0 191 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH NH₂ SH SH — — — H 0 0 192 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₆OH NH₂ SH SH — — — H 0 0 193 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₈OH NH₂ SH SH — — — H 0 0 194 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃NN₂ NH₂ SH SH — — — H 0 0 195 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₆NH₂ NH₂ SH SH — — — H 0 0 196 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPh NH₂ SH SH — — — H 0 0 197 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OBn NH₂ SH SH — — — H 0 0 198 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OMe NH₂ SH SH — — — H 0 0 199 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OEt NH₂ SH SH — — — H 0 0 200 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPt NH₂ SH SH — — — H 0 0 201 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Gly NH₂ SH SH — — — H 0 0 202 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Me NH₂ SH SH — — — H 0 0 203 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Et NH₂ SH SH — — — H 0 0 204 K¹⁻¹ K¹⁻¹ K¹⁻¹ — CH₂OH NH₂ SH SH — — — H 0 0 205 K¹⁻¹ K¹⁻¹ K¹⁻¹ — C₂H₄OH NH₂ SH SH — — — H 0 0 206 K¹⁻¹ K¹⁻¹ K¹⁻¹ — Ph NH₂ SH SH — — — H 0 0 207 K¹⁻¹ K¹⁻¹ K¹⁻¹ — CH₂Ph NH₂ SH SH — — — H 0 0 208 K¹⁻¹ K¹⁻¹ K¹⁻¹ — NH₂ NH₂ SH SH — — — H 0 0 209 K¹⁻¹ K¹⁻¹ K¹⁻¹ — NHPh NH₂ SH SH — — — H 0 0 210 K¹⁻¹ K¹⁻¹ K¹⁻¹ — N(Me)₂ NH₂ SH SH — — — H 0 0 211 K¹⁻¹ K¹⁻¹ K¹⁻¹ — N(Et)₂ NH₂ SH SH — — — H 0 0 212 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SMe NH₂ SH SH — — — H 0 0 213 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SEt NH₂ SH SH — — — H 0 0 214 K¹⁻¹ K¹⁻¹ K¹⁻² — SPh NH₂ SH SH — — — H 0 0 215 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₃OH OH SH SH — — — H 0 0 216 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₄OH OH SH SH — — — H 0 0 217 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₆OH OH SH SH — — — H 0 0 218 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₈OH OH SH SH — — — H 0 0 219 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₃NH₂ OH SH SH — — — H 0 0 220 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₆NH₂ OH SH SH — — — H 0 0 221 K¹⁻¹ K¹⁻¹ K¹⁻² — OPh OH SH SH — — — H 0 0 222 K¹⁻¹ K¹⁻¹ K¹⁻² — OBn OH SH SH — — — H 0 0 223 K¹⁻¹ K¹⁻¹ K¹⁻² — OMe OH SH SH — — — H 0 0 224 K¹⁻¹ K¹⁻¹ K¹⁻² — OEt OH SH SH — — — H 0 0 225 K¹⁻¹ K¹⁻¹ K¹⁻² — OPr OH SH SH — — — H 0 0 226 K¹⁻¹ K¹⁻¹ K¹⁻² — Gly OH SH SH — — — H 0 0 227 K¹⁻¹ K¹⁻¹ K¹⁻² — Me OH SH SH — — — H 0 0 228 K¹⁻¹ K¹⁻¹ K¹⁻² — Et OH SH SH — — — H 0 0 229 K¹⁻¹ K¹⁻¹ K¹⁻² — CH₂OH OH SH SH — — — H 0 0 230 K¹⁻¹ K¹⁻¹ K¹⁻² — C₂H₄OH OH SH SH — — — H 0 0 231 K¹⁻¹ K¹⁻¹ K¹⁻² — Ph OH SH SH — — — H 0 0 232 K¹⁻¹ K¹⁻¹ K¹⁻² — CH₂Ph OH SH SH — — — H 0 0 233 K¹⁻¹ K¹⁻¹ K¹⁻² — NH₂ OH SH SH — — — H 0 0 234 K¹⁻¹ K¹⁻¹ K¹⁻² — NHPh OH SH SH — — — H 0 0 235 K¹⁻¹ K¹⁻¹ K¹⁻² — N(Me)₂ OH SH SH — — — H 0 0 236 K¹⁻¹ K¹⁻¹ K¹⁻² — N(Et)₂ OH SH SH — — — H 0 0 237 K¹⁻¹ K¹⁻¹ K¹⁻² — SMe OH SH SH — — — H 0 0 238 K¹⁻¹ K¹⁻¹ K¹⁻² — SEt OH SH SH — — — H 0 0 239 K¹⁻¹ K¹⁻¹ K¹⁻² — SPh OH SH SH — — — H 0 0 240 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₃OH SH SH SH — — — H 0 0 241 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₄OH SH SH SH — — — H 0 0 242 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₆OH SH SH SH — — — H 0 0 243 K¹⁻¹ K¹⁻¹ K¹⁻² — O(OH₂)₈OH SH SH SH — — — H 0 0 244 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₃NH₂ SH SH SH — — — H 0 0 245 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₆NH₂ SH SH SH — — — H 0 0 246 K¹⁻¹ K¹⁻¹ K¹⁻² — OPh SH SH SH — — — H 0 0 247 K¹⁻¹ K¹⁻¹ K¹⁻² — OBn SH SH SH — — — H 0 0 248 K¹⁻¹ K¹⁻¹ K¹⁻² — OMe SH SH SH — — — H 0 0 249 K¹⁻¹ K¹⁻¹ K¹⁻² — OEt SH SH SH — — — H 0 0 250 K¹⁻¹ K¹⁻¹ K¹⁻² — OPr SH SH SH — — — H 0 0 251 K¹⁻¹ K¹⁻¹ K¹⁻² — Gly SH SH SH — — — H 0 0 252 K¹⁻¹ K¹⁻¹ K¹⁻² — Me SH SH SH — — — H 0 0 253 K¹⁻¹ K¹⁻¹ K¹⁻² — Et SH SH SH — — — H 0 0 254 K¹⁻¹ K¹⁻¹ K¹⁻² — CH₂OH SH SH SH — — — H 0 0 255 K¹⁻¹ K¹⁻¹ K¹⁻² — C₂H₄OH SH SH SH — — — H 0 0 256 K¹⁻¹ K¹⁻¹ K¹⁻² — Ph SH SH SH — — — H 0 0 257 K¹⁻¹ K¹⁻¹ K¹⁻² — CH₂Ph SH SH SH — — — H 0 0 258 K¹⁻¹ K¹⁻¹ K¹⁻² — NH₂ SH SH SH — — — H 0 0 259 K¹⁻¹ K¹⁻¹ K¹⁻² — NHPh SH SH SH — — — H 0 0 260 K¹⁻¹ K¹⁻¹ K¹⁻² — N(Me)₂ SH SH SH — — — H 0 0 261 K¹⁻¹ K¹⁻¹ K¹⁻² — N(Et)₂ SH SH SH — — — H 0 0 262 K¹⁻¹ K¹⁻¹ K¹⁻² — SMe SH SH SH — — — H 0 0 263 K¹⁻¹ K¹⁻¹ K¹⁻² — SEt SH SH SH — — — H 0 0 264 K¹⁻¹ K¹⁻¹ K¹⁻² — SPh SH SH SH — — — H 0 0 265 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₃OH NH₂ SH SH — — — H 0 0 266 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₄OH NH₂ SH SH — — — H 0 0 267 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₆OH NH₂ SH SH — — — H 0 0 268 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₈OH NH₂ SH SH — — — H 0 0 269 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₃NH₂ NH₂ SH SH — — — H 0 0 270 K¹⁻¹ K¹⁻¹ K¹⁻² — O(CH₂)₆NH₂ NH₂ SH SH — — — H 0 0 271 K¹⁻¹ K¹⁻¹ K¹⁻² — OPh NH₂ SH SH — — — H 0 0 272 K¹⁻¹ K¹⁻¹ K¹⁻² — OBn NH₂ SH SH — — — H 0 0 273 K¹⁻¹ K¹⁻¹ K¹⁻² — OMe NH₂ SH SH — — — H 0 0 274 K¹⁻¹ K¹⁻¹ K¹⁻² — OEt NH₂ SH SH — — — H 0 0 275 K¹⁻¹ K¹⁻¹ K¹⁻² — OPr NH₂ SH SH — — — H 0 0 276 K¹⁻¹ K¹⁻¹ K¹⁻² — Gly NH₂ SH SH — — — H 0 0 277 K¹⁻¹ K¹⁻¹ K¹⁻² — Me NH₂ SH SH — — — H 0 0 278 K¹⁻¹ K¹⁻¹ K¹⁻² — Et NH₂ SH SH — — — H 0 0 279 K¹⁻¹ K¹⁻¹ K¹⁻² — CH₂OH NH₂ SH SH — — — H 0 0 280 K¹⁻¹ K¹⁻¹ K¹⁻² — C₂H₄OH NH₂ SH SH — — — H 0 0 281 K¹⁻¹ K¹⁻¹ K¹⁻² — Ph NH₂ SH SH — — — H 0 0 282 K¹⁻¹ K¹⁻¹ K¹⁻² — CH₂Ph NH₂ SH SH — — — H 0 0 283 K¹⁻¹ K¹⁻¹ K¹⁻² — NH₂ NH₂ SH SH — — — H 0 0 284 K¹⁻¹ K¹⁻¹ K¹⁻² — NHPh NH₂ SH SH — — — H 0 0 285 K¹⁻¹ K¹⁻¹ K¹⁻² — N(Me)₂ NH₂ SH SH — — — H 0 0 286 K¹⁻¹ K¹⁻¹ K¹⁻² — N(Et)₂ NH₂ SH SH — — — H 0 0 287 K¹⁻¹ K¹⁻¹ K¹⁻² — SMe NH₂ SH SH — — — H 0 0 288 K¹⁻¹ K¹⁻¹ K¹⁻² — SEt NH₂ SH SH — — — H 0 0 289 K¹⁻¹ K¹⁻¹ K¹⁻² — SPh NH₂ SH SH — — — H 0 0 290 K²⁻¹ K¹⁻¹ K³⁻¹ — OH POMS OH OH — — — H 0 0 291 K²⁻¹ K¹⁻¹ K³⁻¹ — OH POMO OH OH — — — H 0 0 292 K²⁻¹ K¹⁻¹ K³⁻¹ — OH POMS POMS POMS — — — H 0 0 293 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH POMS OH OH — — — H 0 0 294 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH POMO POMO POMO — — — H 0 0 295 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH POMS POMO POMO — — — H 0 0 296 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH POMS POMS POMS — — — H 0 0 297 K²⁻¹ K¹⁻¹ K³⁻² — OH POMS OH OH — — — H 0 0 298 K²⁻¹ K¹⁻¹ K³⁻² — OH POMO OH OH — — — H 0 0 299 K²⁻¹ K¹⁻¹ K³⁻² — OH POMS POMS POMS — — — H 0 0 300 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH POMS OH OH — — — H 0 0 301 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH POMO POMO POMO — — — H 0 0 302 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH POMS POMO POMO — — — H 0 0 303 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH POMS POMS POMS — — — H 0 0 304 K¹⁻¹ K¹⁻¹ K¹⁻¹ — POMO POMO POMO POMO — — — H 0 0 305 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH POMO POMO POMO — — — H 0 0 306 K¹⁻¹ K¹⁻¹ K¹⁻¹ — POMO POMS POMS POMS — — — H 0 0 307 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH POMS POMS POMS — — — H 0 0 308 K¹⁻¹ K¹⁻¹ K¹⁻¹ — POMO POMS POMO POMO — — — H 0 0 309 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH POMS POMO POMO — — — H 0 0 310 K¹⁻¹ K¹⁻¹ K¹⁻¹ — POMO POMO SH SH — — — H 0 0 311 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH POMO SH SH — — — H 0 0 312 K¹⁻¹ K¹⁻¹ K¹⁻¹ — POMO POMS SH SH — — — H 0 0 313 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH POMS SH SH — — — H 0 0 314 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH POMO POMO — — — H 0 0 315 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH POMO POMO — — — H 0 0 316 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH POMO POMO POMO — — — H 0 0 317 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH POMS POMO POMO — — — H 0 0 318 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH POMO POMS POMS — — — H 0 0 319 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH POMS POMS POMS — — — H 0 0 320 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH POMS POMS — — — H 0 0 321 K²⁻¹ K¹⁻¹ K³⁻¹ — OH ATEO OH OH — — — H 0 0 322 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH ATEO OH — — — H 0 0 323 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH ATEO — — — H 0 0 324 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH ATEO ATEO — — — H 0 0 325 K²⁻¹ K¹⁻¹ K³⁻¹ — OH ATEO ATEO ATEO — — — H 0 0 326 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH ATEO OH OH — — — H 0 0 327 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH ATEO OH — — — H 0 0 328 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH ATEO — — — H 0 0 329 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH ATEO ATEO — — — H 0 0 330 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH ATEO ATEO ATEO — — — H 0 0 331 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH ATEO OH — — — H 0 0 332 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH ATEO — — — H 0 0 333 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH ATEO ATEO — — — H 0 0 334 K²⁻¹ K¹⁻¹ K³⁻¹ — OH ATES OH OH — — — H 0 0 335 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH ATES OH — — — H 0 0 336 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH ATES — — — H 0 0 337 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH ATES ATES — — — H 0 0 338 K²⁻¹ K¹⁻¹ K³⁻¹ — OH ATES ATES ATES — — — H 0 0 339 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH ATES OH OH — — — H 0 0 340 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH ATES OH — — — H 0 0 341 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH ATES — — — H 0 0 342 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH ATES ATES — — — H 0 0 343 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH ATES ATES ATES — — — H 0 0 344 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH ATES OH — — — H 0 0 345 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH ATES — — — H 0 0 346 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH ATES ATES — — — H 0 0 347 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH ATEO SH SH — — — H 0 0 348 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH ATEO SH — — — H 0 0 349 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH ATEO — — — H 0 0 350 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH ATEO ATEO — — — H 0 0 351 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH ATEO ATEO ATEO — — — H 0 0 352 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH ATEO SH SH — — — H 0 0 353 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH ATEO SH — — — H 0 0 354 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH ATEO — — — H 0 0 355 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH ATEO ATEO — — — H 0 0 356 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH ATEO ATEO ATEO — — — H 0 0 357 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH ATEO SH — — — H 0 0 358 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH ATEO — — — H 0 0 359 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH ATEO ATEO — — — H 0 0 360 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH ATES SH SH — — — H 0 0 361 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH ATES SH — — — H 0 0 362 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH ATES — — — H 0 0 363 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH ATES ATES — — — H 0 0 364 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH ATES ATES ATES — — — H 0 0 365 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH ATES SH SH — — — H 0 0 366 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH ATES SH — — — H 0 0 367 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH ATES — — — H 0 0 368 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH ATES ATES — — — H 0 0 369 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH ATES ATES ATES — — — H 0 0 370 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH ATES SH — — — H 0 0 371 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH ATES — — — H 0 0 372 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH ATES ATES — — — H 0 0 373 K²⁻¹ K¹⁻¹ K³⁻¹ — OH PTEO OH OH — — — H 0 0 374 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH PTEO OH — — — H 0 0 375 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH PTEO — — — H 0 0 376 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH PTEO PTEO — — — H 0 0 377 K²⁻¹ K¹⁻¹ K³⁻¹ — OH PTEO PTEO PTEO — — — H 0 0 378 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH PTEO OH OH — — — H 0 0 379 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH PTEO OH — — — H 0 0 380 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH PTEO — — — H 0 0 381 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH PTEO PTEO — — — H 0 0 382 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH PTEO PTEO PTEO — — — H 0 0 383 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH PTEO OH — — — H 0 0 384 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH PTEO — — — H 0 0 385 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH PTEO PTEO — — — H 0 0 386 K²⁻¹ K¹⁻¹ K³⁻¹ — OH PTES OH OH — — — H 0 0 387 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH PTES OH — — — H 0 0 388 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH PTES — — — H 0 0 389 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH PTES PTES — — — H 0 0 390 K²⁻¹ K¹⁻¹ K³⁻¹ — OH PTES PTES PTES — — — H 0 0 391 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH PTES OH OH — — — H 0 0 392 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH PTES OH — — — H 0 0 393 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH PTES — — — H 0 0 394 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH PTES PTES — — — H 0 0 395 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH PTES PTES PTES — — — H 0 0 396 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH PTES OH — — — H 0 0 397 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH PTES — — — H 0 0 398 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH PTES PTES — — — H 0 0 399 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH PTEO SH SH — — — H 0 0 400 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH PTEO SH — — — H 0 0 401 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH PTEO — — — H 0 0 402 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH PTEO PTEO — — — H 0 0 403 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH PTEO PTEO PTEO — — — H 0 0 404 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH PTEO SH SH — — — H 0 0 405 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH PTEO SH — — — H 0 0 406 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH PTEO — — — H 0 0 407 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH PTEO PTEO — — — H 0 0 408 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH PTEO PTEO PTEO — — — H 0 0 409 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH PTEO SH — — — H 0 0 410 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH PTEO — — — H 0 0 411 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH PTEO PTEO — — — H 0 0 412 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH PTES SH SH — — — H 0 0 413 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH PTES SH — — — H 0 0 414 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH PTES — — — H 0 0 415 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH PTES PTES — — — H 0 0 416 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH PTES PTES PTES — — — H 0 0 417 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH PTES SH SH — — — H 0 0 418 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH PTES SH — — — H 0 0 419 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH PTES — — — H 0 0 420 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH PTES PTES — — — H 0 0 421 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH PTES PTES PTES — — — H 0 0 422 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH PTES SH — — — H 0 0 423 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH PTES — — — H 0 0 424 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH PTES PTES — — — H 0 0 425 K²⁻¹ K¹⁻¹ K³⁻¹ — OPh ALM OH OH — — — H 0 0 426 K²⁻¹ K¹⁻¹ K³⁻¹ — OPh ALM ALM OH — — — H 0 0 427 K²⁻¹ K¹⁻¹ K³⁻¹ — OPh ALM OH ALM — — — H 0 0 428 K²⁻¹ K¹⁻¹ K³⁻¹ — OPh ALM ALM ALM — — — H 0 0 429 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH ALM ALM — — — H 0 0 430 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH ALM — — — H 0 0 431 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH ALM OH — — — H 0 0 432 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH ALM ALM — — — H 0 0 433 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH ALM — — — H 0 0 434 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH ALM OH — — — H 0 0 435 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH ALM ALM — — — H 0 0 436 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH OH ALM — — — H 0 0 437 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH ALM OH — — — H 0 0 438 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPh ALM SH SH — — — H 0 0 439 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPh ALM ALM SH — — — H 0 0 440 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPh ALM SH ALM — — — H 0 0 441 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OPh ALM ALM ALM — — — H 0 0 442 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH ALM ALM — — — H 0 0 443 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH ALM — — — H 0 0 444 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH ALM SH — — — H 0 0 445 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH ALM ALM — — — H 0 0 446 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH ALM — — — H 0 0 447 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH ALM SH — — — H 0 0 448 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH ALM ALM — — — H 0 0 449 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH ALM — — — H 0 0 450 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH ALM SH — — — H 0 0 451 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻¹ 0 2 452 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON¹⁻¹ 0 2 453 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON¹⁻¹ 0 2 454 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON¹⁻¹ 1 2 455 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON¹⁻¹ 0 2 456 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻¹ 0 1 457 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON¹⁻¹ 0 1 458 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON¹⁻¹ 0 1 459 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON¹⁻¹ 1 1 460 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON¹⁻¹ 0 1 461 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻² 0 2 462 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON¹⁻² 0 2 463 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON¹⁻² 0 2 464 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON¹⁻² 1 2 465 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON¹⁻² 0 2 466 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻² 0 1 467 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON¹⁻² 0 1 468 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON¹⁻² 0 1 469 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON¹⁻² 1 1 470 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON¹⁻² 0 1 471 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻³ 0 2 472 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON¹⁻³ 0 2 473 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON¹⁻³ 0 2 474 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON¹⁻³ 1 2 475 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON¹⁻³ 0 2 476 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻³ 0 1 477 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON¹⁻³ 0 1 478 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON¹⁻³ 0 1 479 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON¹⁻³ 1 1 480 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON¹⁻³ 0 1 481 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻⁴ 0 2 482 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON¹⁻⁴ 0 2 483 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON¹⁻⁴ 0 2 484 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON¹⁻⁴ 1 2 485 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON¹⁻⁴ 0 2 486 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻⁴ 0 1 487 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON¹⁻⁴ 0 1 488 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON¹⁻⁴ 0 1 489 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON¹⁻⁴ 1 1 490 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON¹⁻⁴ 0 1 491 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻⁵ 0 2 492 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON¹⁻⁵ 0 2 493 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON¹⁻⁵ 0 2 494 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON¹⁻⁵ 1 2 495 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON¹⁻⁵ 0 2 496 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻⁵ 0 1 497 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON¹⁻⁵ 0 1 498 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON¹⁻⁵ 0 1 499 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON¹⁻⁵ 1 1 500 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON¹⁻⁵ 0 1 501 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻¹ 0 2 502 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON²⁻¹ 0 2 503 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON²⁻¹ 0 2 504 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON²⁻¹ 1 2 505 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON²⁻¹ 0 2 506 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻¹ 0 1 507 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON²⁻¹ 0 1 508 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON²⁻¹ 0 1 509 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON²⁻¹ 1 1 510 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON²⁻¹ 0 1 511 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻² 0 2 512 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON²⁻² 0 2 513 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON²⁻² 0 2 514 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON²⁻² 1 2 515 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON²⁻² 0 2 516 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻² 0 1 517 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON²⁻² 0 1 518 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON²⁻² 0 1 519 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON²⁻² 1 1 520 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON²⁻² 0 1 521 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻³ 0 2 522 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON²⁻³ 0 2 523 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON²⁻³ 0 2 524 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON²⁻³ 1 2 525 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON²⁻³ 0 2 526 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻³ 0 1 527 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON²⁻³ 0 1 528 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON²⁻³ 0 1 529 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON²⁻³ 1 1 530 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON²⁻³ 0 1 531 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻⁴ 0 2 532 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON²⁻⁴ 0 2 533 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON²⁻⁴ 0 2 534 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON²⁻⁴ 1 2 535 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON²⁻⁴ 0 2 536 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻⁴ 0 1 537 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON²⁻⁴ 0 1 538 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON²⁻⁴ 0 1 539 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON²⁻⁴ 1 1 540 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON²⁻⁴ 0 1 541 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻⁵ 0 2 542 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON²⁻⁵ 0 2 543 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON²⁻⁵ 0 2 544 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON²⁻⁵ 1 2 545 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON²⁻⁵ 0 2 546 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻⁵ 0 1 547 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON²⁻⁵ 0 1 548 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON²⁻⁵ 0 1 549 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON²⁻⁵ 1 1 550 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON²⁻⁵ 0 1 551 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻¹ 0 2 552 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻¹ 0 2 553 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻¹ 0 2 554 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON³⁻¹ 1 2 555 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻¹ 0 2 556 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON³⁻¹ 0 1 557 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON³⁻¹ 0 1 558 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON³⁻¹ 0 1 559 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON³⁻¹ 1 1 560 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON³⁻¹ 0 1 561 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻² 0 2 562 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻² 0 2 563 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻² 0 2 564 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON³⁻² 1 2 565 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻² 0 2 566 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON³⁻² 0 1 567 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON³⁻² 0 1 568 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON³⁻² 0 1 569 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON³⁻² 1 1 570 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON³⁻² 0 1 571 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻³ 0 2 572 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻³ 0 2 573 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻³ 0 2 574 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON³⁻³ 1 2 575 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻³ 0 2 576 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON³⁻³ 0 1 577 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON³⁻³ 0 1 578 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON³⁻³ 0 1 579 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON³⁻³ 1 1 580 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON³⁻³ 0 1 581 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻⁴ 0 2 582 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻⁴ 0 2 583 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻⁴ 0 2 584 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH SH OH L¹ ON³⁻⁴ 1 2 585 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻⁴ 0 2 586 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH₂H₄OH OH OH OH — OH L¹ ON³⁻⁴ 0 1 587 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻⁴ 0 1 588 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻⁴ 0 1 589 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH SH OH L¹ ON³⁻⁴ 1 1 590 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻⁴ 0 1 591 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻⁵ 0 2 592 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻⁵ 0 2 593 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻⁵ 0 2 594 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH SH OH L¹ ON³⁻⁵ 1 2 595 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻⁵ 0 2 596 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻⁵ 0 1 597 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻⁵ 0 1 598 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻⁵ 0 1 599 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH SH OH L¹ ON³⁻⁵ 1 1 600 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻⁵ 0 1 601 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻¹ 0 2 602 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁴⁻¹ 0 2 603 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁴⁻¹ 0 2 604 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁴⁻¹ 1 2 605 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁴⁻¹ 0 2 606 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻¹ 0 1 607 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁴⁻¹ 0 1 608 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁴⁻¹ 0 1 609 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁴⁻¹ 1 1 610 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁴⁻¹ 0 1 611 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻² 0 2 612 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁴⁻² 0 2 613 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁴⁻² 0 2 614 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁴⁻² 1 2 615 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁴⁻² 0 2 616 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻² 0 1 617 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁴⁻² 0 1 618 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁴⁻² 0 1 619 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁴⁻² 1 1 620 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁴⁻² 0 1 621 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻³ 0 2 622 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁴⁻³ 0 2 623 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁴⁻³ 0 2 624 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁴⁻³ 1 2 625 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁴⁻³ 0 2 626 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻³ 0 1 627 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁴⁻³ 0 1 628 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁴⁻³ 0 1 629 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁴⁻³ 1 1 630 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁴⁻³ 0 1 631 K³⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻⁴ 0 2 632 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁴⁻⁴ 0 2 633 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁴⁻⁴ 0 2 634 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁴⁻⁴ 1 2 635 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁴⁻⁴ 0 2 636 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻⁴ 0 1 637 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁴⁻⁴ 0 1 638 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁴⁻⁴ 0 1 639 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁴⁻⁴ 1 1 640 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁴⁻⁴ 0 1 641 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻⁵ 0 2 642 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁴⁻⁵ 0 2 643 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁴⁻⁵ 0 2 644 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁴⁻⁵ 1 2 645 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁴⁻⁵ 0 2 646 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻⁵ 0 1 647 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁴⁻⁵ 0 1 648 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁴⁻⁵ 0 1 649 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁴⁻⁵ 1 1 650 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁴⁻⁵ 0 1 651 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻¹ 0 2 652 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁵⁻¹ 0 2 653 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁵⁻¹ 0 2 654 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁵⁻¹ 1 2 655 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁵⁻¹ 0 2 656 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻¹ 0 1 657 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁵⁻¹ 0 1 658 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁵⁻¹ 0 1 659 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁵⁻¹ 1 1 660 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁵⁻¹ 0 1 661 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻² 0 2 662 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁵⁻² 0 2 663 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁵⁻² 0 2 664 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁵⁻² 1 2 665 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁵⁻² 0 2 666 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻² 0 1 667 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁵⁻² 0 1 668 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁵⁻² 0 1 669 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁵⁻² 1 1 670 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁵⁻² 0 1 671 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻³ 0 2 672 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁵⁻³ 0 2 673 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁵⁻³ 0 2 674 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁵⁻³ 1 2 675 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁵⁻³ 0 2 676 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻³ 0 1 677 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁵⁻³ 0 1 678 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁵⁻³ 0 1 679 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁵⁻³ 1 1 680 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁵⁻³ 0 1 681 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻⁴ 0 2 682 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁵⁻⁴ 0 2 683 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁵⁻⁴ 0 2 684 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁵⁻⁴ 1 2 685 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁵⁻⁴ 0 2 686 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻⁴ 0 1 687 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁵⁻⁴ 0 1 688 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁵⁻⁴ 0 1 689 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁵⁻⁴ 0 1 690 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁵⁻⁴ 0 1 691 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻⁵ 0 2 692 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁵⁻⁵ 0 2 693 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁵⁻⁵ 0 2 694 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁵⁻⁵ 0 2 695 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁵⁻⁵ 0 2 696 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻⁵ 0 1 697 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁵⁻⁵ 0 1 698 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁵⁻⁵ 0 1 699 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁵⁻⁵ 0 1 700 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁵⁻⁵ 0 1 701 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻¹ 0 2 702 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁶⁻¹ 0 2 703 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁶⁻¹ 0 2 704 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₄H₄OH OH SH SH SH OH L¹ ON⁶⁻¹ 0 2 705 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁶⁻¹ 0 2 706 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻¹ 0 1 707 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁶⁻¹ 0 1 708 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁶⁻¹ 0 1 709 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁶⁻¹ 1 1 710 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁶⁻¹ 0 1 711 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻² 0 2 712 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁶⁻² 0 2 713 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁶⁻² 0 2 714 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁶⁻² 1 2 715 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁶⁻² 0 2 716 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻² 0 1 717 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁶⁻² 0 1 718 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁶⁻² 0 1 719 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁶⁻² 1 1 720 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁶⁻² 0 1 721 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻³ 0 2 722 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁶⁻³ 0 2 723 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁶⁻³ 0 2 724 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁶⁻³ 1 2 725 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁶⁻³ 0 2 726 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻³ 0 1 727 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁶⁻³ 0 1 728 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁶⁻³ 0 1 729 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁶⁻³ 1 1 730 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁶⁻³ 0 1 731 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻⁴ 0 2 732 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁶⁻⁴ 0 2 733 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁶⁻⁴ 0 2 734 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁶⁻⁴ 1 2 735 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁶⁻⁴ 0 2 736 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻⁴ 0 1 737 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁶⁻⁴ 0 1 738 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁶⁻⁴ 0 1 739 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁶⁻⁴ 1 1 740 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SH SH SH OH — OH L² ON⁶⁻⁴ 0 1 741 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻⁵ 0 2 742 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁶⁻⁵ 0 2 743 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁶⁻⁵ 0 2 744 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁶⁻⁵ 1 2 745 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁶⁻⁵ 0 2 746 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻⁵ 0 1 747 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁶⁻⁵ 0 1 748 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁶⁻⁵ 0 1 749 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁶⁻⁵ 1 1 750 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁶⁻⁵ 0 1 751 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻¹ 0 2 752 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁷⁻¹ 0 2 753 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁷⁻¹ 0 2 754 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁷⁻¹ 1 2 755 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁷⁻¹ 0 2 756 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻¹ 0 1 757 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁷⁻¹ 0 1 758 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁷⁻¹ 0 1 759 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁷⁻¹ 1 1 760 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁷⁻¹ 0 1 761 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻² 0 2 762 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁷⁻² 0 2 763 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁷⁻² 0 2 764 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁷⁻² 1 2 765 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁷⁻² 0 2 766 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻² 0 1 767 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁷⁻² 0 1 768 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁷⁻² 0 1 769 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH SH OH L² ON⁷⁻² 1 1 770 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁷⁻² 0 1 771 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻³ 0 2 772 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁷⁻³ 0 2 773 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁷⁻³ 0 2 774 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH SH OH L¹ ON⁷⁻³ 1 2 775 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁷⁻³ 0 2 776 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻³ 0 1 777 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁷⁻³ 0 1 778 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁷⁻³ 0 1 779 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH SH OH L² ON⁷⁻³ 1 1 780 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁷⁻³ 0 1 781 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻⁴ 0 2 782 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁷⁻⁴ 0 2 783 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁷⁻⁴ 0 2 784 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH SH OH L¹ ON⁷⁻⁴ 1 2 785 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁷⁻⁴ 0 2 786 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻⁴ 0 1 787 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁷⁻⁴ 0 1 788 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁷⁻⁴ 0 1 789 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁷⁻⁴ 1 1 790 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁷⁻⁴ 0 1 791 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻⁵ 0 2 792 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁷⁻⁵ 0 2 793 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁷⁻⁵ 0 2 794 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁷⁻⁵ 1 2 795 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁷⁻⁵ 0 2 796 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻⁵ 0 1 797 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁷⁻⁵ 0 1 798 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁷⁻⁵ 0 1 799 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁷⁻⁵ 1 1 800 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁷⁻⁵ 0 1 801 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻¹ 0 2 802 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁸⁻¹ 0 2 803 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁸⁻¹ 0 2 804 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁸⁻¹ 1 2 805 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁸⁻¹ 0 2 806 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻¹ 0 1 807 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁸⁻¹ 0 1 808 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁸⁻¹ 0 1 809 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁸⁻¹ 1 1 810 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁸⁻¹ 0 1 811 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻² 0 2 812 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁸⁻² 0 2 813 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁸⁻² 0 2 814 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁸⁻² 1 2 815 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁸⁻² 0 2 816 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻² 0 1 817 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁸⁻² 0 1 818 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁸⁻² 0 1 819 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁸⁻² 1 1 820 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁸⁻² 0 1 821 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻³ 0 2 822 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁸⁻³ 0 2 823 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁸⁻³ 0 2 824 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁸⁻³ 1 2 825 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁸⁻³ 0 2 826 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻³ 0 1 827 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁸⁻³ 0 1 828 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁸⁻³ 0 1 829 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁸⁻³ 1 1 830 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁸⁻³ 0 1 831 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻⁴ 0 2 832 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁸⁻⁴ 0 2 833 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁸⁻⁴ 0 2 834 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁸⁻⁴ 1 2 835 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁸⁻⁴ 0 2 836 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻⁴ 0 1 837 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁸⁻⁴ 0 1 838 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁸⁻⁴ 0 1 839 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁸⁻⁴ 1 1 840 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁸⁻⁴ 0 1 841 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻⁵ 0 2 842 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁸⁻⁵ 0 2 843 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁸⁻⁵ 0 2 844 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁸⁻⁵ 1 2 845 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁸⁻⁵ 0 2 846 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻⁵ 0 1 847 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁸⁻⁵ 0 1 848 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁸⁻⁵ 0 1 849 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁸⁻⁵ 1 1 850 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁸⁻⁵ 0 1 851 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻¹ 0 2 852 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁹⁻¹ 0 2 853 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁹⁻¹ 0 2 854 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁹⁻¹ 1 2 855 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁹⁻¹ 0 2 856 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻¹ 0 1 857 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁹⁻¹ 0 1 858 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁹⁻¹ 0 1 859 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁹⁻¹ 1 1 860 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁹⁻¹ 0 1 861 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻² 0 2 862 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁹⁻² 0 2 863 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁹⁻² 0 2 864 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁹⁻² 1 2 865 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁹⁻² 0 2 866 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻² 0 1 867 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁹⁻² 0 1 868 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁹⁻² 0 1 869 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁹⁻² 1 1 870 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁹⁻² 0 1 871 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻³ 0 2 872 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁹⁻³ 0 2 873 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁹⁻³ 0 2 874 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁹⁻³ 1 2 875 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁹⁻³ 0 2 876 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻³ 0 1 877 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁹⁻³ 0 1 878 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁹⁻³ 0 1 879 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁹⁻³ 1 1 880 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁹⁻³ 0 1 881 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻⁴ 0 2 882 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁹⁻⁴ 0 2 883 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁹⁻⁴ 0 2 884 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁹⁻⁴ 1 2 885 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁹⁻⁴ 0 2 886 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻⁴ 0 1 887 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁹⁻⁴ 0 1 888 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁹⁻⁴ 0 1 889 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁹⁻⁴ 1 1 890 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁹⁻⁴ 0 1 891 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻⁵ 0 2 892 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁹⁻⁵ 0 2 893 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁹⁻⁵ 0 2 894 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁹⁻⁵ 1 2 895 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁹⁻⁵ 0 2 896 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻⁵ 0 1 897 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁹⁻⁵ 0 1 898 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁹⁻⁵ 0 1 899 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁹⁻⁵ 1 1 900 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁹⁻⁵ 0 1 901 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH POMS OH — — — H — — 902 K²⁻¹ K¹⁻¹ K³⁻¹ — OH POMS POMS OH — — — H — — 903 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH POMS POMS OH — — — H — — 904 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH POMS OH — — — H — — 905 K²⁻¹ K¹⁻¹ K³⁻² — OH POMS POMS OH — — — H — — 906 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH POMS POMS OH — — — H — — 907 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH POMS OH — — — H — — 908 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH POMS POMS OH — — — H — — 909 K¹⁻¹ K¹⁻¹ K³⁻¹ — OH POMS POMS OH — — — H — — 910 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH POMS OH — — — H — — 911 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH POMS POMS OH — — — H — — 912 K¹⁻¹ K¹⁻¹ K³⁻² — OH POMS POMS OH — — — H — — 913 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH POMS — — — H — — 914 K²⁻¹ K¹⁻¹ K¹⁻¹ — OH POMS OH POMS — — — H — — 915 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH POMS OH POMS — — — H — — 916 K²⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH OH OH POMS — — — H — — 917 K²⁻¹ K¹⁻¹ K¹⁻² — OH POMS OH POMS — — — H — — 918 K²⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH POMS OH POMS — — — H — — 919 K²⁻¹ K¹⁻¹ K³⁻¹ — OH ATES ATES OH — — — H — — 920 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH ATES ATES OH — — — H — — 921 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH ATES OH — — — H — — 922 K²⁻¹ K¹⁻¹ K³⁻² — OH ATES ATES OH — — — H — — 923 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH ATES ATES OH — — — H — — 924 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH ATES OH — — — H — — 925 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH ATES ATES OH — — — H — — 926 K¹⁻¹ K¹⁻¹ K³⁻¹ — OH ATES ATES OH — — — H — — 927 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH ATES OH — — — H — — 928 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH ATES ATES OH — — — H — — 929 K¹⁻¹ K¹⁻¹ K³⁻² — OH ATES ATES OH — — — H — — 930 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH ATES — — — H — — 931 K²⁻¹ K¹⁻¹ K¹⁻¹ — OH ATES OH ATES — — — H — — 932 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH ATES OH ATES — — — H — — 933 K²⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH OH OH ATES — — — H — — 934 K²⁻¹ K¹⁻¹ K¹⁻² — OH ATES OH ATES — — — H — — 935 K²⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH ATES OH ATES — — — H — — 936 K²⁻¹ K¹⁻¹ K³⁻¹ — OH PTES PTES OH — — — H — — 937 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH PTES PTES OH — — — H — — 938 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH PTES OH — — — H — — 939 K²⁻¹ K¹⁻¹ K³⁻² — OH PTES PTES OH — — — H — — 940 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH PTES PTES OH — — — H — — 941 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH PTES OH — — — H — — 942 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH PTES PTES OH — — — H — — 943 K¹⁻¹ K¹⁻¹ K³⁻¹ — OH PTES PTES OH — — — H — — 944 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH PTES OH — — — H — — 945 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH PTES PTES OH — — — H — — 946 K¹⁻¹ K¹⁻¹ K³⁻² — OH PTES PTES OH — — — H — — 947 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH PTES — — — H — — 948 K²⁻¹ K¹⁻¹ K¹⁻¹ — OH PTES OH PTES — — — H — — 949 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH PTES OH PTES — — — H — — 950 K²⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH OH PTES — — — H — — 951 K²⁻¹ K¹⁻¹ K¹⁻¹ — OH PTES OH PTES — — — H — — 952 K²⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH PTES OH PTES — — — H — — 953 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH SH OH — — — H 0 0 954 K¹⁻¹ K¹⁻¹ K³⁻¹ — OH SH SH OH — — — H 0 0 955 K²⁻¹ K¹⁻¹ K³⁻¹ — OH POMS SH OH — — — H 0 0 956 K¹⁻¹ K¹⁻¹ K³⁻¹ — OH POMS SH OH — — — H 0 0 957 K²⁻¹ K¹⁻¹ K³⁻¹ — OH ATES SH OH — — — H 0 0 958 K¹⁻¹ K¹⁻¹ K³⁻¹ — OH ATES SH OH — — — H 0 0 959 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SH OH OH OH — — — H 0 0 960 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SH OH SH OH — — — H 0 0 961 K²⁻¹ K¹⁻¹ K⁴⁻³ — SH OH OH OH — — — H 0 0 962 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SH OH SH OH — — — H 0 0 963 K²⁻¹ K¹⁻¹ K²⁻¹ — SH OH OH SH — — — H 0 0 964 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄OC(O)tBu OH OH OH — — — H 0 0 965 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄OC(O)Ph OH OH OH — — — H 0 0 966 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C²⁰ OH OH OH — — — H 0 0 967 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁸ OH OH OH — — — H 0 0 968 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁴ OH OH OH — — — H 0 0 969 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁰ OH OH OH — — — H 0 0 970 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C²⁰ OH OH OH — — — H 0 0 971 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁸ OH OH OH — — — H 0 0 972 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁴ OH OH OH — — — H 0 0 973 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁰ OH OH OH — — — H 0 0 974 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C²⁰ OH OH OH — — — H 0 0 975 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁸ OH OH OH — — — H 0 0 976 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁴ OH OH OH — — — H 0 0 977 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁰ OH OH OH — — — H 0 0 978 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C²⁰ OH SH OH — — — H 0 0 979 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁸ OH SH OH — — — H 0 0 980 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁴ OH SH OH — — — H 0 0 981 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁰ OH SH OH — — — H 0 0 982 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C²⁰ OH SH OH — — — H 0 0 983 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁸ OH SH OH — — — H 0 0 984 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁴ OH SH OH — — — H 0 0 985 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁰ OH SH OH — — — H 0 0 986 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C²⁰ OH SH OH — — — H 0 0 987 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁸ OH SH OH — — — H 0 0 988 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁴ OH SH OH — — — H 0 0 989 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁰ OH SH OH — — — H 0 0 990 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C²⁰ OH OH OH — — — H 0 0 991 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁸ OH OH OH — — — H 0 0 992 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁴ OH OH OH — — — H 0 0 993 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁰ OH OH OH — — — H 0 0 994 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C²⁰ OH OH OH — — — H 0 0 995 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁸ OH OH OH — — — H 0 0 996 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁴ OH OH OH — — — H 0 0 997 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁰ OH OH OH — — — H 0 0 998 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁰ OH OH OH — — — H 0 0 999 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁸ OH OH OH — — — H 0 0 1000 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁴ OH OH OH — — — H 0 0 1001 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁰ OH OH OH — — — H 0 0 1002 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C²⁰ OH SH OH — — — H 0 0 1003 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁸ OH SH OH — — — H 0 0 1004 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁴ OH SH OH — — — H 0 0 1005 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁰ OH SH OH — — — H 0 0 1006 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C²⁰ OH SH OH — — — H 0 0 1007 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁸ OH SH OH — — — H 0 0 1008 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁴ OH SH OH — — — H 0 0 1009 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁰ OH SH OH — — — H 0 0 1010 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C²⁰ OH SH OH — — — H 0 0 1011 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁸ OH SH OH — — — H 0 0 1012 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁴ OH SH OH — — — H 0 0 1013 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁰ OH SH OH — — — H 0 0 1014 K²⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C²⁰ OH OH OH — — — H 0 0 1015 K²⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁸ OH OH OH — — — H 0 0 1016 K²⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁴ OH OH OH — — — H 0 0 1017 K²⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁰ OH OH OH — — — H 0 0 1018 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C²⁰ OH OH OH — — — H 0 0 1019 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁸ OH OH OH — — — H 0 0 1020 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁴ OH OH OH — — — H 0 0 1021 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁰ OH OH OH — — — H 0 0 1022 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C²⁰ OH OH OH — — — H 0 0 1023 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁸ OH OH OH — — — H 0 0 1024 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁴ OH OH OH — — — H 0 0 1025 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁰ OH OH OH — — — H 0 0 1026 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C²⁰ OH SH OH — — — H 0 0 1027 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁸ OH SH OH — — — H 0 0 1028 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁴ OH SH OH — — — H 0 0 1029 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁰ OH SH OH — — — H 0 0 1030 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C²⁰ OH SH OH — — — H 0 0 1031 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁸ OH SH OH — — — H 0 0 1032 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁴ OH SH OH — — — H 0 0 1033 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁰ OH SH OH — — — H 0 0 1034 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C²⁰ OH SH OH — — — H 0 0 1035 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁸ OH SH OH — — — H 0 0 1036 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁴ OH SH OH — — — H 0 0 1037 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁰ OH SH OH — — — H 0 0 1038 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C²⁰ OH OH SH — — — H 0 0 1039 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C¹⁸ OH OH SH — — — H 0 0 1040 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C¹⁴ OH OH SH — — — H 0 0 1041 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C¹⁰ OH OH SH — — — H 0 0 1042 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃C²⁰ OH OH SH — — — H 0 0 1043 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃C¹⁸ OH OH SH — — — H 0 0 1044 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃C¹⁴ OH OH SH — — — H 0 0 1045 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃C¹⁰ OH OH SH — — — H 0 0 1046 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄C²⁰ OH OH SH — — — H 0 0 1047 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄C¹⁸ OH OH SH — — — H 0 0 1048 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄C¹⁴ OH OH SH — — — H 0 0 1049 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄C¹⁰ OH OH SH — — — H 0 0 1050 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄C²⁰ OH SH SH — — — H 0 0 1051 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄C¹⁸ OH SH SH — — — H 0 0 1052 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄C¹⁴ OH SH SH — — — H 0 0 1053 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄C¹⁰ OH SH SH — — — H 0 0 1054 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₃C²⁰ OH SH SH — — — H 0 0 1055 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₃C¹⁸ OH SH SH — — — H 0 0 1056 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₃C¹⁴ OH SH SH — — — H 0 0 1057 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₃C¹⁰ OH SH SH — — — H 0 0 1058 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₄C²⁰ OH SH SH — — — H 0 0 1059 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₄C¹⁸ OH SH SH — — — H 0 0 1060 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₄C¹⁴ OH SH SH — — — H 0 0 1061 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₄C¹⁰ OH SH SH — — — H 0 0 1062 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄C²⁰ OH SH SH SH — — H 1 0 1063 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄C¹⁸ OH SH SH SH — — H 1 0 1064 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄C¹⁴ OH SH SH SH — — H 1 0 1065 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄C¹⁰ OH SH SH SH — — H 1 0 1066 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₃C²⁰ OH SH SH SH — — H 1 0 1067 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₃C¹⁸ OH SH SH SH — — H 1 0 1068 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₃C¹⁴ OH SH SH SH — — H 1 0 1069 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₃C¹⁰ OH SH SH SH — — H 1 0 1070 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₄C²⁰ OH SH SH SH — — H 1 0 1071 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₄C¹⁸ OH SH SH SH — — H 1 0 1072 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₄C¹⁴ OH SH SH SH — — H 1 0 1073 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₄C¹⁰ OH SH SH SH — — H 1 0 1074 K²⁻¹ K¹⁻¹ K³⁻¹ — OH SH OH OH — OH S H 0 1 1075 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH S H 0 1 1076 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH OH OH — OH S H 0 1 1077 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH OH OH — OH S H 0 1 1078 K¹⁻¹ K¹⁻¹ K³⁻¹ — OH SH SH OH — OH S H 0 1 1079 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH OH — OH S H 0 1 1080 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH SH OH — OH S H 0 1 1081 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH SH OH — OH S H 0 1 1082 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OH SH OH OH — OH S H 0 1 1083 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH S H 0 1 1084 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH OH OH — OH S H 0 1 1085 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH OH OH — OH S H 0 1 1086 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OH SH SH OH — OH S H 0 1 1087 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH OH — OH S H 0 1 1088 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH SH OH — OH S H 0 1 1089 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH SH OH — OH S H 0 1 1090 K²⁻¹ K¹⁻¹ K⁴⁻³ — OH SH OH OH — OH S H 0 1 1091 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH OH OH — OH S H 0 1 1092 K²⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH OH OH — OH S H 0 1 1093 K²⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH OH OH — OH S H 0 1 1094 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OH SH SH OH — OH S H 0 1 1095 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH OH — OH S H 0 1 1096 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH SH OH — OH S H 0 1 1097 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH SH OH — OH S H 0 1 1098 K²⁻¹ K¹⁻¹ K²⁻¹ — OH SH OH SH — OH S H 0 1 1099 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH SH — OH S H 0 1 1100 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₃OH OH OH SH — OH S H 0 1 1101 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₄OH OH OH SH — OH S H 0 1 1102 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH S H 0 1 1103 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH S H 0 1 1104 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃OH OH SH SH — OH S H 0 1 1105 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH OH SH SH — OH S H 0 1 1106 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OH SH SH SH SH OH S H 1 1 1107 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH S H 1 1 1108 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₃OH OH SH SH SH OH S H 1 1 1109 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₄OH OH SH SH SH OH S H 1 1 1110 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C²⁰ O H 0 1 1111 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁸ O H 0 1 1112 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁴ O H 0 1 1113 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁰ O H 0 1 1114 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C²⁰ O H 0 1 1115 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁸ O H 0 1 1116 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁴ O H 0 1 1117 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁰ O H 0 1 1118 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C²⁰ O H 0 1 1119 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁸ O H 0 1 1120 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁴ O H 0 1 1121 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁰ O H 0 1 1122 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄C²⁰ O H 0 1 1123 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁸ O H 0 1 1124 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁴ O H 0 1 1125 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁰ O H 0 1 1126 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C²⁰ O H 0 1 1127 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁸ O H 0 1 1128 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁴ O H 0 1 1129 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁰ O H 0 1 1130 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C²⁰ O H 0 1 1131 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁸ O H 0 1 1132 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁴ O H 0 1 1133 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁰ O H 0 1 1134 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C²⁰ O H 0 1 1135 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁸ O H 0 1 1136 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁴ O H 0 1 1137 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁰ O H 0 1 1138 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C²⁰ O H 0 1 1139 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁸ O H 0 1 1140 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁴ O H 0 1 1141 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁰ O H 0 1 1142 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C²⁰ O H 0 1 1143 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁸ O H 0 1 1144 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁴ O H 0 1 1145 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁰ O H 0 1 1146 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄C²⁰ O H 0 1 1147 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁸ O H 0 1 1148 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁴ O H 0 1 1149 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁰ O H 0 1 1150 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C²⁰ O H 0 1 1151 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁸ O H 0 1 1152 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁴ O H 0 1 1153 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁰ O H 0 1 1154 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C²⁰ O H 0 1 1155 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁸ O H 0 1 1156 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁴ O H 0 1 1157 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁰ O H 0 1 1158 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH OH OH — SC₂H₄C²⁰ O H 0 1 1159 K²⁻² K¹⁻² K⁴⁻³ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁸ O H 0 1 1160 K²⁻³ K¹⁻³ K⁴⁻³ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁴ O H 0 1 1161 K²⁻⁴ K¹⁻⁴ K⁴⁻³ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁰ O H 0 1 1162 K²⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C²⁰ O H 0 1 1163 K²⁻² K¹⁻² K⁴⁻³ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁸ O H 0 1 1164 K²⁻³ K¹⁻³ K⁴⁻³ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁴ O H 0 1 1165 K²⁻⁴ K¹⁻⁴ K⁴⁻³ — O(CH₂)₃OH OH OH OH — S(CH₂)₃C¹⁰ O H 0 1 1166 K²⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C²⁰ O H 0 1 1167 K²⁻² K¹⁻² K⁴⁻³ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁸ O H 0 1 1168 K²⁻³ K¹⁻³ K⁴⁻³ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁴ O H 0 1 1169 K²⁻⁴ K¹⁻⁴ K⁴⁻³ — O(CH₂)₄OH OH OH OH — S(CH₂)₄C¹⁰ O H 0 1 1170 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH OH — SC₂H₄C²⁰ O H 0 1 1171 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁸ O H 0 1 1172 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁴ O H 0 1 1173 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁰ O H 0 1 1174 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C²⁰ O H 0 1 1175 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁸ O H 0 1 1176 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁴ O H 0 1 1177 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH SH OH — S(CH₂)₃C¹⁰ O H 0 1 1178 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C²⁰ O H 0 1 1179 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁸ O H 0 1 1180 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁴ O H 0 1 1181 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH SH OH — S(CH₂)₄C¹⁰ O H 0 1 1182 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄C²⁰ O H 0 1 1183 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄C¹⁸ O H 0 1 1184 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄C¹⁴ O H 0 1 1185 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄C¹⁰ O H 0 1 1186 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₃OH OH OH SH — S(CH₂)₃C²⁰ O H 0 1 1187 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₃OH OH OH SH — S(CH₂)₃C¹⁸ O H 0 1 1188 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₃OH OH OH SH — S(CH₂)₃C¹⁴ O H 0 1 1189 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₃OH OH OH SH — S(CH₂)₃C¹⁰ O H 0 1 1190 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₄OH OH OH SH — S(CH₂)₄C²⁰ O H 0 1 1191 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₄OH OH OH SH — S(CH₂)₄C¹⁸ O H 0 1 1192 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₄OH OH OH SH — S(CH₂)₄C¹⁴ O H 0 1 1193 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₄OH OH OH SH — S(CH₂)₄C¹⁰ O H 0 1 1194 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1195 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1196 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁴ O H 0 1 1197 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁰ O H 0 1 1198 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃OH OH SH SH — S(CH₂)₃C²⁰ O H 0 1 1199 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃OH OH SH SH — S(CH₂)₃C¹⁸ O H 0 1 1200 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃OH OH SH SH — S(CH₂)₃C¹⁴ O H 0 1 1201 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃OH OH SH SH — S(CH₂)₃C¹⁰ O H 0 1 1202 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH OH SH SH — S(cH₂)₄C²⁰ O H 0 1 1203 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH OH SH SH — S(CH₂)₄C¹⁸ O H 0 1 1204 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH OH SH SH — S(CH₂)₄C¹⁴ O H 0 1 1205 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH OH SH SH — S(CH₂)₄C¹⁰ O H 0 1 1206 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH SC₂H₄C²⁰ O H 1 1 1207 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH SC₂H₄C¹⁸ O H 1 1 1208 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH SC₂H₄C¹⁴ O H 1 1 1209 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH SC₂H₄C¹⁰ O H 1 1 1210 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₃OH OH SH SH SH S(CH₂)₃C²⁰ O H 1 1 1211 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₃OH OH SH SH SH S(CH₂)₃C¹⁸ O H 1 1 1212 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₃OH OH SH SH SH S(CH₂)₃C¹⁴ O H 1 1 1213 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₃OH OH SH SH SH S(CH₂)₃C¹⁰ O H 1 1 1214 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₄OH OH SH SH SH S(CH₂)₄C²⁰ O H 1 1 1215 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₄OH OH SH SH SH S(CH₂)₄C¹⁸ O H 1 1 1216 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₄OH OH SH SH SH S(CH₂)₄C¹⁴ O H 1 1 1217 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₄OH OH SH SH SH S(CH₂)₄C¹⁰ O H 1 1 1218 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C²⁰ OH OH OH — SC₂H₄C²⁰ O H 0 1 1219 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁸ OH OH OH — SC₂H₄C¹⁸ O H 0 1 1220 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁴ OH OH OH — SC₂H₄C¹⁴ O H 0 1 1221 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁰ OH OH OH — SC₂H₄C¹⁰ O H 0 1 1222 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C²⁰ OH OH OH — S(CH₂)₃C²⁰ O H 0 1 1223 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁸ OH OH OH — S(CH₂)₃C¹⁸ O H 0 1 1224 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁴ OH OH OH — S(CH₂)₃C¹⁴ O H 0 1 1225 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁰ OH OH OH — S(CH₂)₃C¹⁰ O H 0 1 1226 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C²⁰ OH OH OH — S(CH₂)₄C²⁰ O H 0 1 1227 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁸ OH OH OH — S(CH₂)₄C¹⁸ O H 0 1 1228 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁴ OH OH OH — S(CH₂)₄C¹⁴ O H 0 1 1229 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁰ OH OH OH — S(CH₂)₄C¹⁰ O H 0 1 1230 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C²⁰ OH SH OH — SC₂H₄C²⁰ O H 0 1 1231 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁸ OH SH OH — SC₂H₄C¹⁸ O H 0 1 1232 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁴ OH SH OH — SC₂H₄C¹⁴ O H 0 1 1233 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄C¹⁰ OH SH OH — SC₂H₄C¹⁰ O H 0 1 1234 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C²⁰ OH SH OH — S(CH₂)₃C²⁰ O H 0 1 1235 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁸ OH SH OH — S(CH₂)₃C¹⁸ O H 0 1 1236 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁴ OH SH OH — S(CH₂)₃C¹⁴ O H 0 1 1237 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃C¹⁰ OH SH OH — S(CH₂)₃C¹⁰ O H 0 1 1238 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C²⁰ OH SH OH — S(CH₂)₄C²⁰ O H 0 1 1239 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁸ OH SH OH — S(CH₂)₄C¹⁸ O H 0 1 1240 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁴ OH SH OH — S(CH₂)₄C¹⁴ O H 0 1 1241 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄C¹⁰ OH SH OH — S(CH₂)₄C¹⁰ O H 0 1 1242 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C²⁰ OH OH OH — SC₂H₄C²⁰ O H 0 1 1243 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁸ OH OH OH — SC₂H₄C¹⁸ O H 0 1 1244 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁴ OH OH OH — SC₂H₄C¹⁴ O H 0 1 1245 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁰ OH OH OH — SC₂H₄C¹⁰ O H 0 1 1246 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C²⁰ OH OH OH — S(CH₂)₃C²⁰ O H 0 1 1247 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁸ OH OH OH — S(CH₂)₃C¹⁸ O H 0 1 1248 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁴ OH OH OH — S(CH₂)₃C¹⁴ O H 0 1 1249 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁰ OH OH OH — S(CH₂)₃C¹⁰ O H 0 1 1250 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C²⁰ OH OH OH — S(CH₂)₄C²⁰ O H 0 1 1251 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁸ OH OH OH — S(CH₂)₄C¹⁸ O H 0 1 1252 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁴ OH OH OH — S(CH₂)₄C¹⁴ O H 0 1 1253 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁰ OH OH OH — S(CH₂)₄C¹⁰ O H 0 1 1254 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C²⁰ OH SH OH — SC₂H₄C²⁰ O H 0 1 1255 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁸ OH SH OH — SC₂H₄C¹⁸ O H 0 1 1256 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁴ OH SH OH — SC₂H₄C¹⁴ O H 0 1 1257 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄C¹⁰ OH SH OH — SC₂H₄C¹⁰ O H 0 1 1258 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C²⁰ OH SH OH — S(CH₂)₃C²⁰ O H 0 1 1259 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁸ OH SH OH — S(CH₂)₃C¹⁸ O H 0 1 1260 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁴ OH SH OH — S(CH₂)₃C¹⁴ O H 0 1 1261 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃C¹⁰ OH SH OH — S(CH₂)₃C¹⁰ O H 0 1 1262 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C²⁰ OH SH OH — S(CH₂)₄C²⁰ O H 0 1 1263 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁸ OH SH OH — S(CH₂)₄C¹⁸ O H 0 1 1264 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁴ OH SH OH — S(CH₂)₄C¹⁴ O H 0 1 1265 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄C¹⁰ OH SH OH — S(CH₂)₄C¹⁰ O H 0 1 1266 K²⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C²⁰ OH OH OH — SC₂H₄C²⁰ O H 0 1 1267 K²⁻² K¹⁻² K⁴⁻³ — SC₂H₄C¹⁸ OH OH OH — SC₂H₄C¹⁸ O H 0 1 1268 K²⁻³ K¹⁻³ K⁴⁻³ — SC₂H₄C¹⁴ OH OH OH — SC₂H₄C¹⁴ O H 0 1 1269 K²⁻⁴ K¹⁻⁴ K⁴⁻³ — SC₂H₄C¹⁰ OH OH OH — SC₂H₄C¹⁰ O H 0 1 1270 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C²⁰ OH OH OH — S(CH₂)₃C²⁰ O H 0 1 1271 K²⁻² K¹⁻² K⁴⁻³ — S(CH₂)₃C¹⁸ OH OH OH — S(CH₂)₃C¹⁸ O H 0 1 1272 K²⁻³ K¹⁻³ K⁴⁻³ — S(CH₂)₃C¹⁴ OH OH OH — S(CH₂)₃C¹⁴ O H 0 1 1273 K²⁻⁴ K¹⁻⁴ K⁴⁻³ — S(CH₂)₃C¹⁰ OH OH OH — S(CH₂)₃C¹⁰ O H 0 1 1274 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C²⁰ OH OH OH — S(CH₂)₄C²⁰ O H 0 1 1275 K²⁻² K¹⁻² K⁴⁻³ — S(CH₂)₄C¹⁸ OH OH OH — S(CH₂)₄C¹⁸ O H 0 1 1276 K²⁻³ K¹⁻³ K⁴⁻³ — S(CH₂)₄C¹⁴ OH OH OH — S(CH₂)₄C¹⁴ O H 0 1 1277 K²⁻⁴ K¹⁻⁴ K⁴⁻³ — S(CH₂)₄C¹⁰ OH OH OH — S(CH₂)₄C¹⁰ O H 0 1 1278 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C²⁰ OH SH OH — SC₂H₄C²⁰ O H 0 1 1279 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁸ OH SH OH — SC₂H₄C¹⁸ O H 0 1 1280 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁴ OH SH OH — SC₂H₄C¹⁴ O H 0 1 1281 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄C¹⁰ OH SH OH — SC₂H₄C¹⁰ O H 0 1 1282 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C²⁰ OH SH OH — S(CH₂)₃C²⁰ O H 0 1 1283 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁸ OH SH OH — S(CH₂)₃C¹⁸ O H 0 1 1284 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁴ OH SH OH — S(CH₂)₃C¹⁴ O H 0 1 1285 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃C¹⁰ OH SH OH — S(CH₂)₃C¹⁰ O H 0 1 1286 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C²⁰ OH SH OH — S(CH₂)₄C²⁰ O H 0 1 1287 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁸ OH SH OH — S(CH₂)₄C¹⁸ O H 0 1 1288 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁴ OH SH OH — S(CH₂)₄C¹⁴ O H 0 1 1289 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄C¹⁰ OH SH OH — S(CH₂)₄C¹⁰ O H 0 1 1290 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C²⁰ OH OH SH — SC₂H₄C²⁰ O H 0 1 1291 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C¹⁸ OH OH SH — SC₂H₄C¹⁸ O H 0 1 1292 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C¹⁴ OH OH SH — SC₂H₄C¹⁴ O H 0 1 1293 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C¹⁰ OH OH SH — SC₂H₄C¹⁰ O H 0 1 1294 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃C²⁰ OH OH SH — S(CH₂)₃C²⁰ O H 0 1 1295 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃C¹⁸ OH OH SH — S(CH₂)₃C¹⁸ O H 0 1 1296 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃C¹⁴ OH OH SH — S(CH₂)₃C¹⁴ O H 0 1 1297 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃C¹⁰ OH OH SH — S(CH₂)₃C¹⁰ O H 0 1 1298 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄C₂₀ OH OH SH — S(CH₂)₄C²⁰ O H 0 1 1299 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄C¹⁸ OH OH SH — S(CH₂)₄C¹⁸ O H 0 1 1300 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄C¹⁴ OH OH SH — S(CH₂)₄C¹⁴ O H 0 1 1301 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄C¹⁰ OH OH SH — S(CH₂)₄C¹⁰ O H 0 1 1302 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄C²⁰ OH SH SH — SC₂H₄C²⁰ O H 0 1 1303 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄C¹⁸ OH SH SH — SC₂H₄C¹⁸ O H 0 1 1304 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄C¹⁴ OH SH SH — SC₂H₄C¹⁴ O H 0 1 1305 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄C¹⁰ OH SH SH — SC₂H₄C¹⁰ O H 0 1 1306 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₃C²⁰ OH SH SH — S(CH₂)₃C²⁰ O H 0 1 1307 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₃C¹⁸ OH SH SH — S(CH₂)₃C¹⁸ O H 0 1 1308 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₃C¹⁴ OH SH SH — S(CH₂)₃C¹⁴ O H 0 1 1309 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₃C¹⁰ OH SH SH — S(CH₂)₃C¹⁰ O H 0 1 1310 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₄C²⁰ OH SH SH — S(CH₂)₄C²⁰ O H 0 1 1311 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₄C¹⁸ OH SH SH — S(CH₂)₄C¹⁸ O H 0 1 1312 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₄C¹⁴ OH SH SH — S(CH₂)₄C¹⁴ O H 0 1 1313 K¹⁻¹ K¹⁻¹ K¹⁻¹ — S(CH₂)₄C¹⁰ OH SH SH — S(CH₂)₄C¹⁰ O H 0 1 1314 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄C²⁰ OH SH SH SH SC₂H₄C²⁰ O H 1 1 1315 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄C¹⁸ OH SH SH SH SC₂H₄C¹⁸ O H 1 1 1316 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄C¹⁴ OH SH SH SH SC₂H₄C¹⁴ O H 1 1 1317 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄C¹⁰ OH SH SH SH SC₂H₄C¹⁰ O H 1 1 1318 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₃C²⁰ OH SH SH SH S(CH₂)₃C²⁰ O H 1 1 1319 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₃C¹⁸ OH SH SH SH S(CH₂)₃C¹⁸ O H 1 1 1320 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₃C¹⁴ OH SH SH SH S(CH₂)₃C¹⁴ O H 1 1 1321 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₃C¹⁰ OH SH SH SH S(CH₂)₃C¹⁰ O H 1 1 1322 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₄C²⁰ OH SH SH SH S(CH₂)₄C²⁰ O H 1 1 1323 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₄C¹⁸ OH SH SH SH S(CH₂)₄C¹⁸ O H 1 1 1324 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₄C¹⁴ OH SH SH SH S(CH₂)₄C¹⁴ O H 1 1 1325 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ S(CH₂)₄C¹⁰ OH SH SH SH S(CH₂)₄C¹⁰ O H 1 1 1326 K²⁻¹ K¹⁻¹ K³⁻² K¹⁻¹ SC₂H₄C²⁰ OH OH OH — — — H 0 0 1327 K²⁻¹ K¹⁻¹ K³⁻² — SC₂H₄C¹⁸ OH OH OH — — — H 0 0 1328 K¹⁻¹ K¹⁻¹ K³⁻² — SC₂H₄C²⁰ OH SH OH — — — H 0 0 1329 K¹⁻¹ K¹⁻¹ K³⁻² — SC₂H₄C¹⁸ OH SH OH — — — H 0 0 1330 K²⁻¹ K¹⁻¹ K⁴⁻² — SC₂H₄C²⁰ OH OH OH — — — H 0 0 1331 K²⁻¹ K¹⁻¹ K⁴⁻² — SC₂H₄C¹⁸ OH OH OH — — — H 0 0 1332 K¹⁻¹ K¹⁻¹ K⁴⁻² — SC₂H₄C²⁰ OH SH OH — — — H 0 0 1333 K¹⁻¹ K¹⁻¹ K⁴⁻² — SC₂H₄C¹⁸ OH SH OH — — — H 0 0 1334 K²⁻¹ K¹⁻¹ K⁴⁻⁴ — SC₂H₄C²⁰ OH OH OH — — — H 0 0 1335 K²⁻¹ K¹⁻¹ K⁴⁻⁴ — SC₂H₄C¹⁸ OH OH OH — — — H 0 0 1336 K¹⁻¹ K¹⁻¹ K⁴⁻⁴ — SC₂H₄C²⁰ OH SH OH — — — H 0 0 1337 K¹⁻¹ K¹⁻¹ K⁴⁻⁴ — SC₂H₄C¹⁸ OH SH OH — — — H 0 0 1338 K²⁻¹ K¹⁻¹ K²⁻² — SC₂H₄C²⁰ OH OH SH — — — H 0 0 1339 K²⁻¹ K¹⁻¹ K²⁻² — SC₂H₄C¹⁸ OH OH SH — — — H 0 0 1340 K¹⁻¹ K¹⁻¹ K¹⁻² — SC₂H₄C²⁰ OH SH SH — — — H 0 0 1341 K¹⁻¹ K¹⁻¹ K¹⁻² — SC₂H₄C¹⁸ OH SH SH — — — H 0 0 1342 K¹⁻¹ K¹⁻¹ K¹⁻² K¹⁻¹ SC₂H₄C²⁰ OH SH SH SH — — H 1 0 1343 K¹⁻¹ K¹⁻¹ K¹⁻² K¹⁻¹ SC₂H₄C¹⁸ OH SH SH SH — — H 1 0 1344 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH OH OH — SC₂H₄C²⁰ O H 0 1 1345 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH OH OH — SC₂H₄C¹⁸ O H 0 1 1346 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH SH OH — SC₂H₄C²⁰ O H 0 1 1347 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH SH OH — SC₂H₄C¹⁸ O H 0 1 1348 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH OH OH — SC₂H₄C²⁰ O H 0 1 1349 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH OH OH — SC₂H₄C¹⁸ O H 0 1 1350 K¹⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH SH OH — SC₂H₄C²⁰ O H 0 1 1351 K¹⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH SH OH — SC₂H₄C¹⁸ O H 0 1 1352 K²⁻¹ K¹⁻¹ K⁴⁻⁴ — OC₂H₄OH OH OH OH — SC₂H₄C²⁰ O H 0 1 1353 K²⁻¹ K¹⁻² K⁴⁻⁴ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁸ O H 0 1 1354 K¹⁻¹ K¹⁻¹ K⁴⁻⁴ — OC₂H₄OH OH SH OH — SC₂H₄C²⁰ O H 0 1 1355 K¹⁻¹ K¹⁻¹ K⁴⁻⁴ — OC₂H₄OH OH SH OH — SC₂H₄C¹⁸ O H 0 1 1356 K²⁻¹ K¹⁻¹ K²⁻² — OC₂H₄OH OH OH SH — SC₂H₄C²⁰ O H 0 1 1357 K²⁻¹ K¹⁻¹ K²⁻² — OC₂H₄OH OH OH SH — SC₂H₄C¹⁸ O H 0 1 1358 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1359 K¹⁻¹ K¹⁻¹ K¹⁻² — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1360 K¹⁻¹ K¹⁻¹ K¹⁻² K¹⁻¹ OC₂H₄OH OH SH SH SH SC₂H₄C²⁰ O H 1 1 1361 K¹⁻¹ K¹⁻¹ K¹⁻² K¹⁻¹ OC₂H₄OH OH SH SH SH SC₂H₄C¹⁸ O H 1 1 1362 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH OH — — — H 0 0 1363 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH OH — — — H 0 0 1364 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — — — H 0 0 1365 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH OH — — — H 0 0 1366 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH OH OH — — — H 0 0 1367 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH OH — — — H 0 0 1368 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH SH — — — H 0 0 1369 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄OH OH OH OH — — — H 0 0 1370 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄OH OH SH OH — — — H 0 0 1371 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄OH OH SH OH — — — H 0 0 1372 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄OH OH OH OH — — — H 0 0 1373 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄OH OH SH OH — — — H 0 0 1374 K²⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄OH OH OH OH — — — H 0 0 1375 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄OH OH SH OH — — — H 0 0 1376 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄OH OH OH SH — — — H 0 0 1377 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃OH OH OH OH — — — H 0 0 1378 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃OH OH SH OH — — — H 0 0 1379 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₃OH OH SH OH — — — H 0 0 1380 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃OH OH OH OH — — — H 0 0 1381 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₃OH OH SH OH — — — H 0 0 1382 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃OH OH OH OH — — — H 0 0 1383 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₃OH OH SH OH — — — H 0 0 1384 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₃OH OH OH SH — — — H 0 0 1385 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄OH OH OH OH — — — H 0 0 1386 K²⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄OH OH SH OH — — — H 0 0 1387 K¹⁻¹ K¹⁻¹ K³⁻¹ — S(CH₂)₄OH OH SH OH — — — H 0 0 1388 K²⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄OH OH OH OH — — — H 0 0 1389 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — S(CH₂)₄OH OH SH OH — — — H 0 0 1390 K²⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄OH OH OH OH — — — H 0 0 1391 K¹⁻¹ K¹⁻¹ K⁴⁻³ — S(CH₂)₄OH OH SH OH — — — H 0 0 1392 K²⁻¹ K¹⁻¹ K²⁻¹ — S(CH₂)₄OH OH OH SH — — — H 0 0 1393 K²⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄OH OH OH OH — SC₂H₄OH O H 0 1 1394 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄OH O H 0 1 1395 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃OH O H 0 1 1396 K²⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄OH O H 0 1 1397 K¹⁻¹ K¹⁻¹ K³⁻¹ — SC₂H₄OH OH SH OH — SC₂H₄OH O H 0 1 1398 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄OH O H 0 1 1399 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃OH O H 0 1 1400 K¹⁻¹ K¹⁻¹ K³⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄OH O H 0 1 1401 K²⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄OH OH OH OH — SC₂H₄OH O H 0 1 1402 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄OH O H 0 1 1403 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH OH OH — S(CH₂)₃OH O H 0 1 1404 K²⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH OH OH — S(CH₂)₄OH O H 0 1 1405 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — SC₂H₄OH OH SH OH — SC₂H₄OH O H 0 1 1406 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH OH — SC₂H₄OH O H 0 1 1407 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₃OH OH SH OH — S(CH₂)₃OH O H 0 1 1408 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — O(CH₂)₄OH OH SH OH — S(CH₂)₄OH O H 0 1 1409 K²⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄OH OH OH OH — SC₂H₄OH O H 0 1 1410 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH OH OH — SC₂H₄OH O H 0 1 1411 K²⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH OH OH — S(CH₂)₃OH O H 0 1 1412 K²⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH OH OH — S(CH₂)₄OH O H 0 1 1413 K¹⁻¹ K¹⁻¹ K⁴⁻³ — SC₂H₄OH OH SH OH — SC₂H₄OH O H 0 1 1414 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH OH — SC₂H₄OH O H 0 1 1415 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₃OH OH SH OH — S(CH₂)₃OH O H 0 1 1416 K¹⁻¹ K¹⁻¹ K⁴⁻³ — O(CH₂)₄OH OH SH OH — S(CH₂)₄OH O H 0 1 1417 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄OH OH OH SH — SC₂H₄OH O H 0 1 1418 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄OH O H 0 1 1419 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₃OH OH OH SH — S(CH₂)₃OH O H 0 1 1420 K²⁻¹ K¹⁻¹ K²⁻¹ — O(CH₂)₄OH OH OH SH — S(CH₂)₄OH O H 0 1 1421 K¹⁻¹ K¹⁻¹ K¹⁻¹ — SC₂H₄OH OH SH SH — SC₂H₄OH O H 0 1 1422 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄OH O H 0 1 1423 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₃OH OH SH SH — S(CH₂)₃OH O H 0 1 1424 K¹⁻¹ K¹⁻¹ K¹⁻¹ — O(CH₂)₄OH OH SH SH — S(CH₂)₄OH O H 0 1 1425 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ SC₂H₄OH OH SH SH SH SC₂H₄OH O H 1 1 1426 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH SC₂H₄OH O H 1 1 1427 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₃OH OH SH SH SH S(CH₂)₃OH O H 1 1 1428 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ O(CH₂)₄OH OH SH SH SH S(CH₂)₄OH O H 1 1 1429 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻⁶ 0 2 1430 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH OH — OH L¹ ON¹⁻⁶ 0 2 1431 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON¹⁻⁶ 0 2 1432 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON¹⁻⁶ 1 2 1433 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON¹⁻⁶ 0 2 1434 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻⁶ 0 1 1435 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON¹⁻⁶ 0 1 1436 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON¹⁻⁶ 0 1 1437 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON¹⁻⁶ 1 1 1438 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON¹⁻⁶ 0 1 1439 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻⁷ 0 2 1440 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON¹⁻⁷ 0 2 1441 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON¹⁻⁷ 0 2 1442 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON¹⁻⁷ 1 2 1443 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON¹⁻⁷ 0 2 1444 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻⁷ 0 1 1445 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON¹⁻⁷ 0 1 1446 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON¹⁻⁷ 0 1 1447 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON¹⁻⁷ 1 1 1448 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON¹⁻⁷ 0 1 1449 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻⁶ 0 2 1450 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON²⁻⁶ 0 2 1451 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON²⁻⁶ 0 2 1452 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON²⁻⁶ 1 2 1453 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON²⁻⁶ 0 2 1454 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻⁶ 0 1 1455 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON²⁻⁶ 0 1 1456 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON²⁻⁶ 0 1 1457 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON²⁻⁶ 1 1 1458 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON²⁻⁶ 0 1 1459 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻⁷ 0 2 1460 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON²⁻⁷ 0 2 1461 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON²⁻⁷ 0 2 1462 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON²⁻⁷ 1 2 1463 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON²⁻⁷ 0 2 1464 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻⁷ 0 1 1465 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON²⁻⁷ 0 1 1466 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON²⁻⁷ 0 1 1467 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON²⁻⁷ 1 1 1468 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON²⁻⁷ 0 1 1469 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻⁶ 0 2 1470 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻⁶ 0 2 1471 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻⁶ 0 2 1472 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON³⁻⁶ 1 2 1473 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻⁶ 0 2 1474 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON³⁻⁶ 0 1 1475 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON³⁻⁶ 0 1 1476 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON³⁻⁶ 0 1 1477 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON³⁻⁶ 1 1 1478 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON³⁻⁶ 0 1 1479 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻⁷ 0 2 1480 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON³⁻⁷ 0 2 1481 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON³⁻⁷ 0 2 1482 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON³⁻⁷ 1 2 1483 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON³⁻⁷ 0 2 1484 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON³⁻⁷ 0 1 1485 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON³⁻⁷ 0 1 1486 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON³⁻⁷ 0 1 1487 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON³⁻⁷ 1 1 1488 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON³⁻⁷ 0 1 1489 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻⁶ 0 2 1490 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁴⁻⁶ 0 2 1491 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁴⁻⁶ 0 2 1492 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁴⁻⁶ 1 2 1493 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁴⁻⁶ 0 2 1494 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻⁶ 0 1 1495 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁴⁻⁶ 0 1 1496 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁴⁻⁶ 0 1 1497 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁴⁻⁶ 1 1 1498 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁴⁻⁶ 0 1 1499 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻⁷ 0 2 1500 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁴⁻⁷ 0 2 1501 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁴⁻⁷ 0 2 1502 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁴⁻⁷ 1 2 1503 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁴⁻⁷ 0 2 1504 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻⁷ 0 1 1505 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁴⁻⁷ 0 1 1506 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁴⁻⁷ 0 1 1507 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁴⁻⁷ 1 1 1508 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁴⁻⁷ 0 1 1509 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻⁶ 0 2 1510 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁵⁻⁶ 0 2 1511 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁵⁻⁶ 0 2 1512 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁵⁻⁶ 1 2 1513 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁵⁻⁶ 0 2 1514 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻⁶ 0 1 1515 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁵⁻⁶ 0 1 1516 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁵⁻⁶ 0 1 1517 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁵⁻⁶ 1 1 1518 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁵⁻⁶ 0 1 1519 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻⁷ 0 2 1520 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁵⁻⁷ 0 2 1521 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁵⁻⁷ 0 2 1522 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁵⁻⁷ 1 2 1523 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁵⁻⁷ 0 2 1524 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻⁷ 0 1 1525 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁵⁻⁷ 0 1 1526 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁵⁻⁷ 0 1 1527 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁵⁻⁷ 1 1 1528 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁵⁻⁷ 0 1 1529 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻⁶ 0 2 1530 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁶⁻⁶ 0 2 1531 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁶⁻⁶ 0 2 1532 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁶⁻⁶ 1 2 1533 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁶⁻⁶ 0 2 1534 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻⁶ 0 1 1535 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁶⁻⁶ 0 1 1536 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁶⁻⁶ 0 1 1537 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁶⁻⁶ 1 1 1538 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁶⁻⁶ 0 1 1539 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻⁷ 0 2 1540 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁶⁻⁷ 0 2 1541 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁶⁻⁷ 0 2 1542 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁶⁻⁷ 1 2 1543 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁶⁻⁷ 0 2 1544 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻⁷ 0 1 1545 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁶⁻⁷ 0 1 1546 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁶⁻⁷ 0 1 1547 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁶⁻⁷ 1 1 1548 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁶⁻⁷ 0 1 1549 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻⁶ 0 2 1550 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁷⁻⁶ 0 2 1551 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁷⁻⁶ 0 2 1552 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁷⁻⁶ 1 2 1553 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁷⁻⁶ 0 2 1554 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻⁶ 0 1 1555 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁷⁻⁶ 0 1 1556 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁷⁻⁶ 0 1 1557 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁷⁻⁶ 1 1 1558 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁷⁻⁶ 0 1 1559 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻⁷ 0 2 1560 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁷⁻⁷ 0 2 1561 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁷⁻⁷ 0 2 1562 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁷⁻⁷ 1 2 1563 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁷⁻⁷ 0 2 1564 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻⁷ 0 1 1565 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁷⁻⁷ 0 1 1566 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁷⁻⁷ 0 1 1567 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁷⁻⁷ 1 1 1568 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁷⁻⁷ 0 1 1569 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻⁶ 0 2 1570 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁸⁻⁶ 0 2 1571 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁸⁻⁶ 0 2 1572 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁸⁻⁶ 1 2 1573 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁸⁻⁶ 0 2 1574 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻⁶ 0 1 1575 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁸⁻⁶ 0 1 1576 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁸⁻⁶ 0 1 1577 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁸⁻⁶ 1 1 1578 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁸⁻⁶ 0 1 1579 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻⁷ 0 2 1580 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁸⁻⁷ 0 2 1581 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁸⁻⁷ 0 2 1582 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁸⁻⁷ 1 2 1583 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁸⁻⁷ 0 2 1584 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻⁷ 0 1 1585 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁸⁻⁷ 0 1 1586 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁸⁻⁷ 0 1 1587 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁸⁻⁷ 1 1 1588 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁸⁻⁷ 0 1 1589 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻⁶ 0 2 1590 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁹⁻⁶ 0 2 1591 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁹⁻⁶ 0 2 1592 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁹⁻⁶ 1 2 1593 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁹⁻⁶ 0 2 1594 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻⁶ 0 1 1595 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁹⁻⁶ 0 1 1596 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁹⁻⁶ 0 1 1597 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁹⁻⁶ 1 1 1598 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁹⁻⁶ 0 1 1599 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻⁷ 0 2 1600 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L¹ ON⁹⁻⁷ 0 2 1601 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L¹ ON⁹⁻⁷ 0 2 1602 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L¹ ON⁹⁻⁷ 1 2 1603 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L¹ ON⁹⁻⁷ 0 2 1604 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻⁷ 0 1 1605 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH OH SH SH — OH L² ON⁹⁻⁷ 0 1 1606 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OC₂H₄OH SH SH SH — OH L² ON⁹⁻⁷ 0 1 1607 K¹⁻¹ K¹⁻¹ K¹⁻¹ K¹⁻¹ OC₂H₄OH OH SH SH SH OH L² ON⁹⁻⁷ 1 1 1608 K¹⁻¹ K¹⁻¹ K¹⁻¹ — OH SH SH SH — OH L² ON⁹⁻⁷ 0 1 1609 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻⁶ 0 2 1610 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻⁶ 0 1 1611 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁻⁷ 0 2 1612 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁻⁷ 0 1 1613 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻⁶ 0 2 1614 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻⁶ 0 1 1615 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON²⁻⁷ 0 2 1616 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON²⁻⁷ 0 1 1617 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻⁶ 0 2 1618 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON³⁻⁶ 0 1 1619 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON³⁻⁷ 0 2 1620 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON³⁻⁷ 0 1 1621 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻⁶ 0 2 1622 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻⁶ 0 1 1623 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁴⁻⁷ 0 2 1624 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁴⁻⁷ 0 1 1625 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻⁶ 0 2 1626 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻⁶ 0 1 1627 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁵⁻⁷ 0 2 1628 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁵⁻⁷ 0 1 1629 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻⁶ 0 2 1630 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻⁶ 0 1 1631 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁶⁻⁷ 0 2 1632 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁶⁻⁷ 0 1 1633 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻⁶ 0 2 1634 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻⁶ 0 1 1635 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁷⁻⁷ 0 2 1636 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁷⁻⁷ 0 1 1637 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻⁶ 0 2 1638 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻⁶ 0 1 1639 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁸⁻⁷ 0 2 1640 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁸⁻⁷ 0 1 1641 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻⁶ 0 2 1642 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻⁶ 0 1 1643 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON⁹⁻⁷ 0 2 1644 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH OH — OH L² ON⁹⁻⁷ 0 1 1645 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH O H 0 1 1646 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH SH — SH O H 0 1 1647 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH O H 0 1 1648 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1649 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄C²⁰ O H 0 1 1650 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1651 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1652 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄C¹⁸ O H 0 1 1653 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1654 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH SH SH — SH O H 0 1 1655 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH OH SH — SH O H 0 1 1656 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH SH SH — SH O H 0 1 1657 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1658 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH OH SH — SC₂H₄C²⁰ O H 0 1 1659 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1660 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1661 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH OH SH — SC₂H₄C¹⁸ O H 0 1 1662 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1663 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH O H 0 1 1664 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH SH — SH O H 0 1 1665 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH O H 0 1 1666 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1667 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄C²⁰ O H 0 1 1668 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1669 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1670 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH OH SH — SC₂H₄C¹⁸ O H 0 1 1671 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1672 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH SH SH — SH O H 0 1 1673 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH OH SH — SH O H 0 1 1674 K¹⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH SH SH — SH O H 0 1 1675 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1676 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH OH SH — SC₂H₄C²⁰ O H 0 1 1677 K¹⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1678 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1679 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH OH SH — SC₂H₄C¹⁸ O H 0 1 1680 K¹⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1681 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH SH — SH O H 0 1 1682 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH OH SH — SH O H 0 1 1683 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH SH — SH O H 0 1 1684 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1685 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH OH SH — SC₂H₄C²⁰ O H 0 1 1686 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1687 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1688 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH OH SH — SC₂H₄C¹⁸ O H 0 1 1689 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1690 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH O H 0 1 1691 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C²⁰ O H 0 1 1692 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄C¹⁸ O H 0 1 1693 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH O H 0 1 1694 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH O H 0 1 1695 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1696 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1697 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1698 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1699 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH SH SH SH — SH O H 0 1 1700 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH SH SH SH — SH O H 0 1 1701 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1702 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1703 K²⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1704 K¹⁻¹ K¹⁻¹ K³⁻² — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1705 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH O H 0 1 1706 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH O H 0 1 1707 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1708 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1709 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1710 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1711 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH SH SH SH — SH O H 0 1 1712 K¹⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH SH SH SH — SH O H 0 1 1713 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1714 K¹⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1715 K²⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1716 K¹⁻¹ K¹⁻¹ K⁴⁻² — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1717 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH SH SH SH — SH O H 0 1 1718 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH SH SH SH — SH O H 0 1 1719 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1720 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1721 K²⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1722 K¹⁻¹ K¹⁻¹ K⁴⁻³ — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1723 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH O H 0 1 1724 K¹⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH O H 0 1 1725 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1726 K¹⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C²⁰ O H 0 1 1727 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1728 K¹⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄C¹⁸ O H 0 1 1729 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁻⁶ 0 2 1730 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁻⁶ 0 2 1731 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁻⁶ 0 2 1732 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁻⁶ 0 2 1733 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁻⁶ 0 2 1734 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁻⁶ 0 2 1735 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁻⁶ 0 2 1736 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁻⁶ 0 2 1737 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁻⁶ 0 2 1738 K¹⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁻⁶ 0 2 1739 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁻⁶ 0 1 1740 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁻⁶ 0 1 1741 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁻⁶ 0 1 1742 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁻⁶ 0 1 1743 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁻⁶ 0 1 1744 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁻⁶ 0 1 1745 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁻⁶ 0 1 1746 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁻⁶ 0 1 1747 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁻⁶ 0 1 1748 K¹⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁻⁶ 0 1 1749 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON²⁻⁶ 0 2 1750 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON²⁻⁶ 0 2 1751 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON²⁻⁶ 0 2 1752 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON²⁻⁶ 0 2 1753 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON²⁻⁶ 0 2 1754 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON²⁻⁶ 0 2 1755 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON²⁻⁶ 0 2 1756 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON²⁻⁶ 0 2 1757 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON²⁻⁶ 0 2 1758 K¹⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON²⁻⁶ 0 2 1759 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON²⁻⁶ 0 1 1760 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON²⁻⁶ 0 1 1761 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON²⁻⁶ 0 1 1762 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON²⁻⁶ 0 1 1763 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON²⁻⁶ 0 1 1764 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON²⁻⁶ 0 1 1765 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON²⁻⁶ 0 1 1766 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON²⁻⁶ 0 1 1767 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON²⁻⁶ 0 1 1768 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON²⁻⁶ 0 1 1769 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON³⁻⁶ 0 2 1770 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON³⁻⁶ 0 2 1771 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON³⁻⁶ 0 2 1772 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON³⁻⁶ 0 2 1773 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON³⁻⁶ 0 2 1774 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON³⁻⁶ 0 2 1775 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON³⁻⁶ 0 2 1776 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON³⁻⁶ 0 2 1777 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON³⁻⁶ 0 2 1778 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON³⁻⁶ 0 2 1779 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON³⁻⁶ 0 1 1780 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON³⁻⁶ 0 1 1781 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON³⁻⁶ 0 1 1782 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON³⁻⁶ 0 1 1783 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON³⁻⁶ 0 1 1784 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON³⁻⁶ 0 1 1785 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON³⁻⁶ 0 1 1786 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON³⁻⁶ 0 1 1787 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON³⁻⁶ 0 1 1788 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON³⁻⁶ 0 1 1789 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1790 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1791 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1792 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1793 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1794 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1795 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1796 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1797 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1798 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁴⁻⁶ 0 2 1799 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁴⁻⁶ 0 1 1800 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁴⁻⁶ 0 1 1801 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁴⁻⁶ 0 1 1802 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁴⁻⁶ 0 1 1803 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁴⁻⁶ 0 1 1804 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁴⁻⁶ 0 1 1805 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁴⁻⁶ 0 1 1806 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁴⁻⁶ 0 1 1807 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁴⁻⁶ 0 1 1808 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁴⁻⁶ 0 1 1809 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1810 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1811 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1812 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1813 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂K₄OH OH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1814 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1815 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1816 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1817 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1818 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁵⁻⁶ 0 2 1819 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁵⁻⁶ 0 1 1820 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁵⁻⁶ 0 1 1821 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁵⁻⁶ 0 1 1822 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁵⁻⁶ 0 1 1823 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁵⁻⁶ 0 1 1824 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁵⁻⁶ 0 1 1825 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁵⁻⁶ 0 1 1826 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁵⁻⁶ 0 1 1827 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁵⁻⁶ 0 1 1828 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁵⁻⁶ 0 1 1829 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1830 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1831 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1832 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1833 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1834 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1835 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1836 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1837 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1838 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁶⁻⁶ 0 2 1839 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁶⁻⁶ 0 1 1840 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁶⁻⁶ 0 1 1841 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁶⁻⁶ 0 1 1842 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁶⁻⁶ 0 1 1843 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁶⁻⁶ 0 1 1844 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁶⁻⁶ 0 1 1845 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁶⁻⁶ 0 1 1846 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁶⁻⁶ 0 1 1847 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁶⁻⁶ 0 1 1848 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁶⁻⁶ 0 1 1849 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1850 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1851 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1852 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1853 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1854 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1855 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1856 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1857 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1858 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁷⁻⁶ 0 2 1859 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁷⁻⁶ 0 1 1860 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁷⁻⁶ 0 1 1861 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁷⁻⁶ 0 1 1862 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁷⁻⁶ 0 1 1863 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁷⁻⁶ 0 1 1864 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁷⁻⁶ 0 1 1865 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁷⁻⁶ 0 1 1866 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁷⁻⁶ 0 1 1867 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁷⁻⁶ 0 1 1868 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁷⁻⁶ 0 1 1869 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1870 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1871 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1872 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1873 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1874 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1875 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1876 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1877 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1878 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁸⁻⁶ 0 2 1879 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁸⁻⁶ 0 1 1880 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁸⁻⁶ 0 1 1881 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁸⁻⁶ 0 1 1882 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁸⁻⁶ 0 1 1883 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁸⁻⁶ 0 1 1884 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁸⁻⁶ 0 1 1885 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁸⁻⁶ 0 1 1886 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁸⁻⁶ 0 1 1887 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁸⁻⁶ 0 1 1888 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁸⁻⁶ 0 1 1889 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1890 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1891 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1892 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1893 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1894 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1895 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1896 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1897 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1898 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON⁹⁻⁶ 0 2 1899 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁹⁻⁶ 0 1 1900 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁹⁻⁶ 0 1 1901 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁹⁻⁶ 0 1 1902 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁹⁻⁶ 0 1 1903 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON⁹⁻⁶ 0 1 1904 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁹⁻⁶ 0 1 1905 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁹⁻⁶ 0 1 1906 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁹⁻⁶ 0 1 1907 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁹⁻⁶ 0 1 1908 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON⁹⁻⁶ 0 1 1909 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1910 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1911 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1912 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1913 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1914 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1915 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1916 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1917 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1918 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L¹ ON¹⁰⁻¹ 0 2 1919 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁰⁻¹ 0 1 1920 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁰⁻¹ 0 1 1921 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁰⁻¹ 0 1 1922 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁰⁻¹ 0 1 1923 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SH L² ON¹⁰⁻¹ 0 1 1924 K²⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁰⁻¹ 0 1 1925 K¹⁻¹ K¹⁻¹ K³⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁰⁻¹ 0 1 1926 K²⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁰⁻¹ 0 1 1927 K¹⁻¹ K¹⁻¹ K⁴⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁰⁻¹ 0 1 1928 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SH L² ON¹⁰⁻¹ 0 1 1929 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹¹⁻¹ 0 2 1930 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹²⁻¹ 0 2 1931 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹³⁻¹ 0 2 1932 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁴⁻¹ 0 2 1933 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁵⁻¹ 0 2 1934 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁶⁻¹ 0 2 1935 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L¹ ON¹⁷⁻¹ 0 2 1936 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — OH L² ON¹⁴⁻¹ 0 1 1937 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — — — H 0 0 1938 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH OH OH — SC₂H₄C¹⁸ O H 0 1 1939 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C²⁰ OH SH SH — — — H 0 0 1940 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C¹⁸ OH SH SH — — — H 0 0 1941 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄OH OH SH SH — — — H 0 0 1942 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C²⁰ SH SH SH — — — H 0 0 1943 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄C¹⁸ SH SH SH — — — H 0 0 1944 K²⁻¹ K¹⁻¹ K²⁻¹ — SC₂H₄OH SH SH SH — — — H 0 0 1945 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH OH SH SH — SC₂H₄OH — H 0 1 1946 K²⁻¹ K¹⁻¹ K²⁻¹ — OC₂H₄OH SH SH SH — SC₂H₄OH — H 0 1

In Table 1, Ph represents a phenyl group, Bn represents a benzyl group, Me represents a methyl group, Et represents an ethyl group, Pr represents an n-propyl group and tBu represents a tert-butyl group; and in Table 1, the groups described as K^(x) represent groups having the following structure.

Further, in Table 1, the groups described as Gly, POMO, POMS, ATE, PTE, ALM, L¹, L², C²⁰, C¹⁸, C¹⁴ and C¹⁰ represent groups having the following structures respectively.

Further, in Table 1, the groups described as ON^(X) represent oligonucleotide analogs having the structures defined below and bonded to R⁷ at the terminal.

ON¹⁻¹

—G^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-G^(e)-p-G^(e)-p-G^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-A^(e)-p-A^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-C^(e)-hp

ON¹⁻²

—G^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-G^(e)-p-G^(e)-p-G^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-A^(e)-p-A^(e)-p-A^(e)-hp

ON¹⁻³

—A^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-A^(e)-p-A^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-C^(e)-hp

ON¹⁻⁴

—G^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-G^(e)-p-G^(n)-s-G^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-C^(n)-s-A^(n)-s-A^(n)-s-A^(n)-s-A^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-C^(e)-hp

ON¹⁻⁵

—G^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-G^(e)-p-G^(n)-s-G^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-C^(e)-p-A^(e)-p-A^(e)-p-A^(e)-p-A^(e)-hp

ON¹⁻⁶

—G^(e)-s-C^(e)-s-G^(e)-s-C^(e)-s-G^(e)-s-G^(n)-s-G^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-C^(n)-s-A^(n)-s-A^(n)-s-A^(n)-s-A^(e)-s-G^(e)-s-C^(e)-s-A^(e)-s-C^(e)-hp

ON¹⁻⁷

—G^(e)-s-C^(e)-s-G^(e)-s-C^(e)-s-G^(e)-s-G^(n)-s-G^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-C^(n)-s-A^(n)-s-A^(n)-s-A^(n)-s-A^(e)-s-G^(e)-s-C^(e)-s-A^(e)-s-C^(e)-hp

ON²⁻¹

—G^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-G^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-T^(e)-hp

ON²⁻²

—C^(e)-p-A^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-G^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-T^(e)-hp

ON²⁻³

—C^(e)-p-A^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-G^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-C^(e)-hp

ON²⁻⁴

—G^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-C^(n)-s-C^(n)-s-G^(n)-s-G^(n)-s-G^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-A^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-T^(e)-hp

ON²⁻⁵

—C^(e)-p-A^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-G^(n)-s-G^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-A^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-T^(e)-hp

ON²⁻⁶

—G^(e)-s-C^(e)-s-C^(e)-s-C^(e)-s-A^(e)-s-C^(n)-s-C^(n)-s-G^(n)-s-G^(n)-s-G^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-A^(e)-s-C^(e)-s-C^(e)-s-A^(e)-s-T^(e)-hp

ON²⁻⁷

—C^(e)-s-A^(e)-s-C^(e)-s-C^(e)-s-G^(e)-s-G^(n)-s-G^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-A^(e)-s-C^(e)-s-C^(e)-s-A^(e)-s-T^(e)-hp

ON³⁻¹

—G^(e)-p-T^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-G^(e)-hp

ON³⁻²

—C^(e)-p-T^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-G^(e)-hp

ON³⁻³

—C^(e)-p-T^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-T^(e)-hp

ON³⁻⁴

—G^(e)-p-T^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-A^(n)-s-C^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-C^(n)-s-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-G^(e)-hp

ON³⁻⁵

—C^(e)-p-T^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-C^(n)-s-C^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-C^(n)-s-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-G^(e)-hp

ON³⁻⁶

—G^(e)-s-T^(e)-s-A^(e)-s-C^(e)-s-T^(e)-s-A^(n)-s-C^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-C^(n)-s-T^(e)-s-T^(e)-s-C^(e)-s-T^(e)-s-G^(e)-hp

ON³⁻⁷

—C^(e)-s-T^(e)-s-A^(e)-s-C^(e)-s-T^(e)-s-C^(n)-s-C^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-C^(n)-s-T^(e)-s-T^(e)-s-C^(e)-s-T^(e)-s-G^(e)-hp

ON⁴⁻¹

—G^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-T^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁴⁻²

—C^(e)-p-T^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-T^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁴⁻³

—C^(e)-p-T^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-T^(e)-p-T^(e)-hp

ON⁴⁻⁴

—G^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-C^(n)-s-G^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-G^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-T^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁴⁻⁵

—C^(e)-p-T^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-T^(n)-s-G^(n)-s-G^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-T^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁴⁻⁶

—G^(e)-s-T^(e)-s-T^(e)-s-C^(e)-s-T^(e)-s-C^(n)-s-G^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-G^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-T^(e)-s-T^(e)-s-T^(e)-s-C^(e)-s-A^(e)-hp

ON⁴⁻⁷

—C^(e)-s-T^(e)-s-C^(e)-s-G^(e)-s-C^(e)-s-T^(n)-s-G^(n)-s-G^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-T^(e)-s-T^(e)-s-T^(e)-s-C^(e)-s-A^(e)-hp

ON⁵⁻¹

—G^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁵⁻²

—C^(e)-p-A^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁵⁻³

—C^(e)-p-A^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-G^(e)-hp

ON⁵⁻⁴

—G^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-A^(n)-s-G^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-G^(n)-s-C^(n)-s-A^(n)-s-T^(n)-s-C^(n)-s-C^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁵⁻⁵

—C^(e)-p-A^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-T^(n)-s-G^(n)-s-G^(n)-s-C^(n)-s-A^(n)-s-T^(n)-s-C^(n)-s-C^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁵⁻⁶

—G^(e)-s-C^(e)-s-C^(e)-s-C^(e)-s-A^(e)-s-A^(n)-s-G^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-G^(n)-s-C^(n)-s-A^(n)-s-T^(n)-s-C^(n)-s-C^(e)-s-G^(e)-s-T^(e)-s-C^(e)-s-A^(e)-hp

ON⁵⁻⁷

—C^(e)-s-A^(e)-s-A^(e)-s-G^(e)-s-C^(e)-s-T^(n)-s-G^(n)-s-G^(n)-s-C^(n)-s-A^(n)-s-T^(n)-s-C^(n)-s-C^(e)-s-G^(e)-s-T^(e)-s-C^(e)-s-A^(e)-hp

ON⁶⁻¹

—T^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-A^(e)-p-G^(e)-p-G^(e)-p-G^(e)-hp

OH⁶⁻²

—G^(e)-p-T^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-A^(e)-p-G^(e)-p-G^(e)-p-G^(e)-hp

ON⁶⁻³

—G^(e)-p-T^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON⁶⁻⁴

—T^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-T^(e)-p-C^(n)-s-A^(n)-s-T^(n)-s-C^(n)-s-G^(n)-s-C^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-T^(n)-s-C^(e)-p-A^(e)-p-G^(e)-p-G^(e)-p-G^(e)-hp

ON⁶⁻⁵

—G^(e)-p-T^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-C^(n)-s-G^(n)-s-C^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-T^(n)-s-C^(e)-p-A^(e)-p-G^(e)-p-G^(e)-p-G^(e)-hp

ON⁶⁻⁶

—T^(e)-s-C^(e)-s-C^(e)-s-G^(e)-s-T^(e)-s-C^(n)-s-A^(n)-s-T^(n)-s-C^(n)-s-G^(n)-s-C^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-T^(n)-s-C^(e)-s-A^(e)-s-G^(e)-s-G^(e)-s-G^(e)-hp

ON⁶⁻⁷

—G^(e)-s-T^(e)-s-C^(e)-s-A^(e)-s-T^(e)-s-C^(n)-s-G^(n)-s-C^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-T^(n)-s-C^(e)-s-A^(e)-s-G^(e)-s-G^(e)-s-G^(e)-hp

ON⁷⁻¹

—G^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-T^(e)-p-T^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-hp

ON⁷⁻²

—G^(e)-p-A^(e)-p-T^(e)-p-T^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-G^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-hp

ON⁷⁻³

—G^(e)-p-A^(e)-p-T^(e)-p-T^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-G^(e)-p-T^(e)-hp

ON⁷⁻⁴

—G^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-T^(n)-s-T^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-G^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-hp

ON⁷⁻⁵

—G^(e)-p-A^(e)-p-T^(e)-p-T^(e)-p-A^(e)-p-G^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-G^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-hp

ON⁷⁻⁶

—G^(e)-s-C^(e)-s-T^(e)-s-G^(e)-s-A^(e)-s-T^(n)-s-T^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-G^(e)-s-T^(e)-s-C^(e)-s-C^(e)-s-C^(e)-hp

ON⁷⁻⁷

—G^(e)-p-A^(e)-p-T^(e)-p-T^(e)-p-A^(e)-p-G^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-A^(n)-s-G^(n)-s-G^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-hp

ON⁸⁻¹

—G^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-C^(e)-hp

ON⁸⁻²

—C^(e)-p-C^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-C^(e)-hp

ON⁸⁻³

—C^(e)-p-C^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-T^(e)-p-C^(e)-p-C^(e)-hp

ON⁸⁻⁴

—G^(e)-p-C^(e)-p-T^(e)-p-C^(e)-p-C^(e)-p-T^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-A^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-T^(n)-s-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-C^(e)-hp

ON⁸⁻⁵

—C^(e)-p-C^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-C^(n)-s-A^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-T^(n)-s-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-C^(e)-hp

ON⁸⁻⁶

—G^(e)-s-C^(e)-s-T^(e)-s-C^(e)-s-C^(e)-s-T^(n)-s-T^(n)-s-C^(n)-s-C^(n)-s-A^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-T^(n)-s-C^(e)-s-C^(e)-s-T^(e)-s-G^(e)-s-C^(e)-hp

ON⁸⁻⁷

—C^(e)-s-C^(e)-s-T^(e)-s-T^(e)-s-C^(e)-s-C^(n)-s-A^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-T^(n)-s-C^(e)-s-C^(e)-s-T^(e)-s-G^(e)-s-C^(e)-hp

ON⁹⁻¹

—T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-T^(e)-hp

ON⁹⁻²

—C^(e)-p-G^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-T^(e)-hp

ON⁹⁻³

—C^(e)-p-G^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(e)-p-T^(e)-p-G^(e)-p-A^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-G^(e)-p-C^(e)-hp

ON⁹⁻⁴

—T^(e)-p-C^(e)-p-C^(e)-p-C^(e)-p-G^(e)-p-C^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-C^(n)-s-A^(n)-s-T^(n)-s-G^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-T^(e)-hp

ON⁹⁻⁵

—C^(e)-p-G^(e)-p-C^(e)-p-C^(e)-p-T^(e)-p-G^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-C^(n)-s-A^(n)-s-T^(n)-s-G^(e)-p-C^(e)-p-A^(e)-p-T^(e)-p-T^(e)-hp

ON⁹⁻⁶

—T^(e)-s-C^(e)-s-C^(e)-s-C^(e)-s-G^(e)-s-C^(n)-s-C^(n)-s-T^(n)-s-G^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-C^(n)-s-A^(n)-s-T^(n)-s-G^(e)-s-C^(e)-s-A^(e)-s-T^(e)-s-T^(e)-hp

ON⁹⁻⁷

—C^(e)-s-G^(e)-s-C^(e)-s-C^(e)-s-T^(e)-s-G^(n)-s-T^(n)-s-G^(n)-s-A^(n)-s-C^(n)-s-A^(n)-s-T^(n)-s-G^(e)-s-C^(e)-s-A^(e)-s-T^(e)-s-T^(e)-hp

ON¹⁰⁻¹

—T^(e)-s-A^(e)-s-G^(e)-s-G^(e)-s-G^(e)-s-T^(e)-s-T^(e)-s-A^(e)-s-G^(e)-s-A^(e)-s-C^(e)-s-A^(e)-s-A^(e)-s-G^(e)-hp

ON¹¹⁻¹

-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-C^(e)-p-C^(n)-p-C^(n)-p-T^(n)-p-G^(n)-p-A^(n)-p-A^(n)-p-C^(n)-p-A^(n)-p-G^(n)-p-T^(n)-p-T^(e)-p-G^(e)-p-A^(e)-p-T^(e)-p-C^(e)-hp

ON¹²⁻¹

-p-T^(e)-p-C^(e)-p-T^(e)-p-T^(e)-p-G^(e)-p-G^(n)-p-T^(n)-p-T^(n)-p-G^(n)-p-T^(n)-p-A^(n)-p-A^(n)-p-G^(n)-p-A^(n)-p-G^(n)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-hp

ON¹³⁻¹

-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-p-G^(e)-p-G^(n)-p-C^(n)-p-C^(n)-p-T^(n)-p-C^(n)-p-C^(n)-p-A^(n)-p-T^(n)-p-A^(n)-p-T^(n)-p-G^(e)-p-G^(e)-p-A^(e)-p-A^(e)-p-T^(e)-hp

ON¹⁴⁻¹

-p-G^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-C^(n)-p-G^(n)-p-C^(n)-p-T^(n)-p-G^(n)-p-G^(n)-p-T^(n)-p-G^(n)-p-A^(n)-p-G^(n)-p-T^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

ON¹⁵⁻¹

-p-G^(e)-p-A^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-A^(n)-p-A^(n)-p-A^(n)-p-T^(n)-p-C^(n)-p-T^(n)-p-C^(n)-p-T^(n)-p-G^(n)-p-C^(n)-p-C^(e)-p-G^(e)-p-C^(e)-p-A^(e)-p-T^(e)-hp

ON¹⁶⁻¹

-p-A^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-C^(e)-p-A^(n)-p-C^(n)-p-C^(n)-p-T^(n)-p-C^(n)-p-T^(n)-p-T^(n)-p-G^(n)-p-T^(n)-p-G^(n)-p-G^(e)-p-A^(e)-p-C^(e)-p-C^(e)-p-A^(e)-hp

ON¹⁷⁻¹

-p-C^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-C^(e)-p-A^(n)-p-T^(n)-p-G^(n)-p-G^(n)-p-T^(n)-p-C^(n)-p-C^(n)-p-C^(n)-p-C^(n)-p-C^(n)-p-C^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-A^(e)-hp

Further, the groups described as A^(n), G^(n), C^(n), T^(n), A^(e), G^(e), C^(e), T^(e), p, s and hp in the above represent groups having the following structure.

In the base sequences of the aforementioned oligonucleotide analogs, ON¹ is a sequence in human telomerase (GenBank Accession No. U86046, base sequence of the complementary chain of nucleotide numbers 170 to 188), ON² is a sequence in human breakpoint cluster region (BCR) mRNA (GenBank Accession No. NM-021574.1, base sequence of the complementary chain of nucleotide numbers 597 to 614), ON³ is a sequence in interferon-inducible double-stranded RNA-dependent human protein kinase (PKR) mRNA (GenBank Accession No. NM-002759.1, base sequence of the complementary chain of nucleotide numbers 490 to 508), ON⁴ is a sequence in human protein kinase C, alpha (PKCα) mRNA (GenBank Accession No. NM-002737.1, base sequence of the complementary chain of nucleotide numbers 2044 to 2063), ON⁵ is a sequence in human intercellular adhesion molecule (ICAM1) mRNA (GenBank Accession No. NM-000201.1, base sequence of the complementary chain of nucleotide numbers 2100 to 2119), ON⁶ is a sequence in human ras transforming protein gene (GenBank Accession No. M38453.1, base sequence of the complementary chain of nucleotide numbers 121 to 140), ON⁷ is a sequence in human tumor necrosis factor (TNF superfamily, member 2) (TNF) mRNA (GenBank Accession No. NM-000594.1, base sequence of the complementary chain of nucleotide numbers 279 to 298), ON⁸ is a sequence in human phosphotyrosyl-protein phosphatase (PTP-1B) mRNA (GenBank Accession No. M31724.1, base sequence of the complementary chain of nucleotide numbers 951 to 970), ON⁹ is a sequence in human c-raf-1 mRNA (GenBank Accession No. NM-002880.1, base sequence of the complementary chain of nucleotide numbers 2484 to 2503), and ON¹⁰ is a sequence in human telomerase mRNA (GenBank Accession No. U86046, base sequence of the complementary chain of nucleotide numbers 136 to 148).

In the above Table 1, the preferred compounds are 1, 2, 3, 4, 5, 6, 7, 8, 13, 22, 27, 28, 31, 39, 41, 42, 50, 52, 53, 61, 63, 64, 71, 73, 77, 79, 96, 98, 102, 104, 146, 148, 152, 154, 171, 173, 177, 179, 290, 292, 293, 305, 307, 310, 311, 312, 313, 314, 316, 319, 320, 325, 330, 334, 338, 339, 343, 344, 351, 356, 364, 369, 377, 382, 386, 390, 391, 395, 396, 403, 408, 416, 421, 424, 425, 428, 438, 441, 451, 452, 453, 454, 455, 461, 462, 463, 464, 465, 471, 472, 473, 474, 475, 481, 482, 483, 484, 485, 491, 492, 493, 494, 495, 501, 502, 503, 504, 505, 511, 512, 513, 514, 515, 521, 522, 523, 524, 525, 531, 532, 533, 534, 535, 541, 542, 543, 544, 545, 551, 552, 553, 554, 555, 561, 562, 563, 564, 565, 571, 572, 573, 574, 575, 581, 582, 583, 584, 585, 591, 592, 593, 594, 595, 601, 602, 603, 604, 605, 611, 612, 613, 614, 615, 621, 622, 623, 624, 625, 631, 632, 633, 634, 635, 641, 642, 643, 644, 645, 651, 652, 653, 654, 655, 661, 662, 663, 664, 665, 671, 672, 673, 674, 675, 681, 682, 683, 684, 685, 691, 692, 693, 694, 695, 701, 702, 703, 704, 705, 711, 712, 713, 714, 715, 721, 722, 723, 724, 725, 731, 732, 733, 734, 735, 741, 742, 743, 744, 745, 751, 752, 753, 754, 755, 761, 762, 763, 764, 765, 771, 772, 773, 774, 775, 781, 782, 783, 784, 785, 791, 792, 793, 794, 795, 801, 802, 803, 804, 805, 811, 812, 813, 814, 815, 821, 822, 823, 824, 825, 831, 832, 833, 834, 835, 841, 842, 843, 844, 845, 851, 852, 853, 854, 855, 861, 862, 863, 864, 865, 871, 872, 873, 874, 875, 881, 882, 883, 884, 885, 891, 892, 893, 894, 895, 901, 902, 903, 907, 908, 909, 913, 914, 915, 919, 920, 924, 925, 926, 930, 931, 932, 936, 937, 941, 942, 943, 947, 948, 949, 953, 954, 959, 960, 961, 962, 963, 966, 967, 978, 979, 990, 991, 1002, 1003, 1014, 1015, 1026, 1027, 1038, 1039, 1050, 1051, 1062, 1063, 1074, 1075, 1078, 1079, 1082, 1083, 1086, 1087, 1090, 1091, 1094, 1095, 1098, 1099, 1102, 1103, 1106, 1107, 1110, 1111, 1122, 1123, 1134, 1135, 1146, 1147, 1158, 1159, 1170, 1171, 1182, 1183, 1194, 1195, 1206, 1207, 1220, 1231, 1243, 1255, 1267, 1279, 1291, 1303, 1315, 1344, 1345, 1346, 1347, 1348, 1349, 1350, 1351, 1352, 1353, 1354, 1355, 1356, 1357, 1358, 1359, 1360, 1361, 1429, 1430, 1431, 1432, 1433, 1449, 1450, 1451, 1452, 1453, 1469, 1470, 1471, 1472, 1473, 1489, 1490, 1491, 1492, 1493, 1509, 1510, 1511, 1512, 1513, 1529, 1530, 1531, 1532, 1533, 1549, 1550, 1551, 1552., 1553, 1569, 1570, 1571, 1572, 1573, 1589, 1590, 1591, 1592, 1593, 1609, 1609, 1613, 1617, 1621, 1625, 1629, 1633, 1637, 1641, 1645, 1647, 1648, 1650, 1651, 1653, 1663, 1665, 1666, 1668, 1669, 1671, 1690, 1691, 1692, 1693, 1694, 1695, 1696, 1697, 1698, 1705, 1706, 1707, 1708, 1709, 1710, 1723, 1724, 1725, 1726, 1727, 1728, 1734, 1735, 1736, 1737, 1738, 1754, 1755, 1756, 1757, 1758, 1774, 1775, 1776, 1777, 1778 1794, 1795, 1796, 1797 1798, 1814, 1815, 1816, 1817, 1818, 1834, 1835, 1836, 1837 1838, 1854, 1855, 1856, 1857, 1858, 1874, 1875, 1876, 1877, 1878, 1894, 1895, 1896, 1897, 1898, 1914, 1915, 1916, 1917, and 1918, and more preferable compounds are 1, 2, 3, 4, 5, 8, 290, 305, 307, 338, 343, 364, 369, 390, 395, 416, 421, 451, 452, 455, 461, 462, 465, 471, 472, 475, 481, 482, 485, 491, 492, 495, 501, 502, 505, 511, 512, 515, 521, 522, 525, 531, 532, 535, 541, 542, 545, 551, 552, 555, 561, 562, 565, 571, 572, 575, 581, 582, 585, 591, 592, 595, 601, 602, 605, 611, 612, 615, 621, 622, 625, 631, 632, 635, 641, 642, 645, 651, 652, 655, 661, 662, 665, 671, 672, 675, 681, 682, 685, 691, 692, 695, 701, 702, 705, 711, 712, 715, 721, 722, 725, 731, 732, 735, 741, 742, 745, 751, 752, 755, 761, 762, 765, 771, 772, 775, 781, 782, 785, 791, 792, 795, 801, 802, 805, 811, 812, 815, 821, 822, 825, 831, 832, 835, 841, 842, 845, 851, 852, 855, 861, 862, 865, 871, 872, 875, 881, 882, 885, 891, 892, 895, 953, 954, 959, 960, 961, 962, 963, 966, 967, 978, 979, 990, 991, 1002, 1003, 1014, 1015, 1026, 1027, 1038, 1039, 1050, 1051, 1062, 1063, 1075, 1079, 1083, 1087, 1091, 1095, 1099, 1103, 1107, 1110, 1111, 1122, 1123, 1134, 1135, 1146, 1147, 1158, 1159, 1170, 1171, 1182, 1183, 1194, 1195, 1206, 1207, 1429, 1430, 1449, 1450, 1469, 1470, 1489, 1490, 1509, 1510, 1529, 1530, 1549, 1550, 1569, 1570, 1589, 1590, 1648, 1650, 1651, 1653, 1666, 1668, 1669, 1671, 1691, 1692, 1695, 1696, 1697, 1698, 1707, 1708, 1709, 1710, 1725, 1726, 1727, and 1728.

The compounds (1) of the present invention can be prepared by appropriately utilizing Process A, Process B, Process C, Process D, Process E, Process F, Process G, and Process H mentioned below.

In Process A, Process B, Process C, Process D, Process E, Process F, Process G, and Process H, A, D, R¹, R⁷, and R⁸ have the same meanings as defined above; R⁹ represents a protecting group for protecting a phosphoric acid group or a phosphorous acid group; R¹⁰ represents a dialkylamino group (particularly a diisopropylamino group or a diethylamino group); R¹¹ represents an R¹ group which requires a protecting group in the synthesis of the 2-5A analog; B¹ represents a purin-9-yl group or a substituted purin-9-yl group having substituent(s) selected from the above Group α, but a group substituted by amino group is excluded. R¹² and R¹⁶ are the same or different and represent a protecting group; R¹³ represents a —(CH₂)h- group (h is an integer of from 2 to 8); R¹⁴ represents a hydroxyl group, a phenyloxy group which may be substituted, or an ethyloxy group which may be substituted by halogen; R¹⁵ represents an oxygen atom, a sulfur atom or an NH group; and HR¹⁵—P (encircled) represents a high molecular weight compound.

The “protecting group” in the definition of R⁹ can be, for example, a lower alkyl group such as methyl; a lower alkenyl group such as 2-propenyl; a cyano lower alkyl group such as 2-cyanoethyl; a lower alkoxylated lower alkoxymethyl group such as 2-methoxyethoxymethyl; a halogeno lower alkoxymethyl group such as 2,2,2-trichloroethoxymethyl and bis(2-chloroethoxy)methyl; a halogenated ethyl group such as 2,2,2-trichloroethyl; a methyl group substituted by an aryl group such as benzyl; a methyl group substituted by from 1 to 3 aryl groups whose aryl ring is substituted by lower alkyl, lower alkoxy, halogen or cyano group(s) such as 4-methylbenzyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl and 4-cyanobenzyl; an aryl group substituted by halogen atom(s), lower alkoxy group(s) or nitro group(s) such as 4-chlorophenyl, 2-chlorophenyl, 4-methoxyphenyl, 4-nitrophenyl and 2,4-dinitrophenyl; or a lower alkylcarbonyloxymethyl group such as pentanoyloxymethyl and pivaloyloxymethyl; and is preferably a methyl group, a 2-cyanoethyl group, a benzyl group, a 2-chlorophenyl group, a 4-chlorophenyl group, a 2-propenyl group or a pivaloyloxymethyl group.

The “protecting group” in the definition of R¹² and R¹⁶ can be, for example, an “acyl type” protecting group including an “aliphatic acyl group” such as an alkylcarbonyl group, e.g., formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, nonanoyl, decanoyl, 3-methylnonanoyl, 8-methylnonanoyl, 3-ethyloctanoyl, 3,7-dimethyloctanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, 1-methylpentadecanoyl, 14-methylpentadecanoyl, 13,13-dimethyltetradecanoyl, heptadecanoyl, 15-methylhexadecanoyl, octadecanoyl, 1-methylheptadecanoyl, nonadecanoyl, eicosanoyl and heneicosanoyl; a carboxylated alkylcarbonyl group, e.g., succinoyl, glutaroyl and adipoyl; a halogeno lower alkylcarbonyl group, e.g., chloroacetyl, dichloroacetyl, trichloroacetyl and trifluoroacetyl; a lower alkoxy lower alkylcarbonyl group, e.g., methoxyacetyl; or an unsaturated alkylcarbonyl group, e.g., (E)-2-methyl-2-butenoyl; and

an “aromatic acyl group” such as an arylcarbonyl group, e.g., benzoyl, α-naphthoyl and β-naphthoyl; a halogeno arylcarbonyl group, e.g., 2-bromobenzoyl and 4-chlorobenzoyl; a lower alkylated arylcarbonyl group, e.g., 2,4,6-trimethylbenzoyl and 4-toluoyl; a lower alkoxylated arylcarbonyl group, e.g., 4-anisoyl; a carboxylated arylcarbonyl group, e.g., 2-carboxybenzoyl, 3-carboxybenzoyl and 4-carboxybenzoyl; a nitrated arylcarbonyl group, e.g., 4-nitrobenzoyl and 2-nitrobenzoyl; a lower alkoxycarbonylated arylcarbonyl group, e.g., 2-(methoxycarbonyl)benzoyl; or an arylated arylcarbonyl group, e.g., 4-phenylbenzoyl;

a “lower alkyl group” such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl and 2-ethylbutyl; a “lower alkenyl group” such as ethenyl, 1-propenyl, 2-propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 2-ethyl-2-propenyl, 1-butenyl, 2-butenyl, 1-methyl-2-butenyl, 1-methyl-1-butenyl, 3-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 1-pentenyl, 2-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl and 5-hexenyl; a “tetrahydropyranyl or tetrahydrothiopyranyl group” such as tetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl and 4-methoxytetrahydrothiopyran-4-yl; a “tetrahydrofuranyl or tetrahydrothiofuranyl group” such as tetrahydrofuran-2-yl and tetrahydrothiofuran-2-yl; a “silyl group” such as a tri-lower alkylsilyl group, e.g., trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl and triisopropylsilyl; or a tri-lower alkylsilyl group substituted by 1 or 2 aryl groups, e.g., diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl and phenyldiisopropylsilyl; a “lower alkoxymethyl group” such as methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl and t-butoxymethyl; a “lower alkoxylated lower alkoxymethyl group” such as 2-methoxyethoxymethyl; a “halogeno lower alkoxymethyl” such as 2,2,2-trichloroethoxymethyl and bis(2-chloroethoxy)methyl; a “lower alkoxylated ethyl group” such as 1-ethoxyethyl and 1-(isopropoxy)ethyl; a “halogenated ethyl group” such as 2,2,2-trichloroethyl; a “methyl group substituted by from 1 to 3 aryl groups” such as benzyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl and 9-anthrylmethyl; a “methyl group substituted by from 1 to 3 aryl groups whose aryl ring is substituted by lower alkyl, lower alkoxy, halogen or cyano group(s)” such as 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 4,4′-dimethoxytriphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl and 4-cyanobenzyl; a “lower alkoxycarbonyl group” such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl and isobutoxycarbonyl; an “aryl group substituted by halogen atom(s), lower alkoxy group(s) or nitro group(s)” such as 4-chlorophenyl, 2-chlorophenyl, 4-methoxyphenyl, 4-nitrophenyl and 2,4-dinitrophenyl; a “lower alkoxycarbonyl group substituted by halogen or tri-lower alkylsilyl group(s)” such as 2,2,2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl; an “alkenyloxycarbonyl group” such as vinyloxycarbonyl and aryloxycarbonyl; or an “aralkyloxycarbonyl group whose aryl ring may be substituted by 1 or 2 lower alkoxy or nitro groups” such as benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl and 4-nitrobenzyloxycarbonyl.

In the following, the respective steps of Process A, Process B, Process C, Process D, Process E, Process F, Process G, and Process H will be explained in detail.

(Step A-1)

The present step is a step, wherein compound (3) is produced by reacting compound (2) with a mono-substituted chloro(alkoxy)phosphine, di-substituted alkoxyphosphine, mono-substituted chloro(benzyloxy)phosphine, or di-substituted benzyloxyphosphine normally used for amidite formation, in an inert solvent.

The solvent to be used is not particularly limited so long as it does not affect the reaction, but can preferably be an ether such as tetrahydrofuran, diethyl ether or dioxane; or a halogenated hydrocarbon such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene.

The mono-substituted chloro(alkoxy)phosphine to be used can be, for example, a phosphine such as chloro(morpholino)methoxyphosphine, chloro(morpholino)cyanoethoxyphosphine, chloro(dimethylamino)methoxyphosphine, chloro(dimethylamino)cyanoethoxyphosphine, chloro(diisopropylamino)methoxyphosphine or chloro(diisopropylamino)cyanoethoxyphosphine, and is preferably chloro(morpholino)methoxyphosphine, chloro(morpholino)cyanoethoxyphosphine, chloro(diisopropylamino)methoxyphosphine or chloro(diisopropylamino)cyanoethoxyphosphine.

In the case of using a mono-substituted chloro(alkoxy)phosphine, a deoxidizer is used. In that case, the deoxidizer to be used can be a heterocyclic amine such as pyridine or dimethylaminopyridine; or an aliphatic amine such as trimethylamine, triethylamine, diisopropylamine or diisopropylethylamine, and is preferably an aliphatic amine (particularly diisopropylethylamine).

The di-substituted alkoxyphosphine to be used can be, for example, a phosphine such as bis(diisopropylamino)cyanoethoxyphosphine, bis(diethylamino)methanesulfonylethoxyphosphine, bis(diisopropylamino)(2,2,2-trichloroethoxy)phosphine or bis(diisopropylamino)(4-chlorophenylmethoxy)phosphine, and is preferably bis(diisopropylamino)cyanoethoxyphosphine.

In the case of using a di-substituted alkoxyphosphine, an acid or an organic salt is used. In that case, the acid to be used is tetrazol, acetic acid or p-toluenesulfonic acid, and the organic salt to be used is tetrazol diisopropylamine salt, acetic acid diisopropylamine salt or p-toluenesulfonic acid diisopropylamine salt, preferably tetrazol or tetrazol diisopropylamine salt.

The mono-substituted chloro(benzyloxy)phosphine to be used can be, for example, a phosphine such as chloro(morpholino)benzyloxyphosphine, chloro(dimethylamino)methoxyphosphine, chloro(dimethylamino)benzyloxyphosphine or chloro(diisopropylamino)benzyloxyphosphine, and is preferably chloro(diisopropylamino)benzyloxyphosphine.

In the case of using a mono-substituted chloro(benzyloxy)phosphine, a deoxidizer is used. In that case, the deoxidizer to be used can be a heterocyclic amine such as pyridine or dimethylaminopyridine; or an aliphatic amine such as trimethylamine, triethylamine, diisopropylamine or diisopropylethylamine, and is preferably an aliphatic amine (particularly diisopropylethylamine).

The di-substituted benzyloxyphosphine to be used can be, for example, a phosphine such as bis(diisopropylamino)benzyloxyphosphine or bis(diethylamino)benzyloxyphosphine, and is preferably bis(diisopropylamino)benzyloxyphosphine.

In the case of using a di-substituted benzyloxyphosphine, an acid or an organic salt is used. In that case, the acid to be used is tetrazol, acetic acid or p-toluenesulfonic acid, and the organic salt to be used is tetrazol diisopropylamine salt, acetic acid diisopropylamine salt or p-toluenesulfonic acid diisopropylamine salt, preferably tetrazol or tetrazol diisopropylamine salt.

The reaction temperature is not particularly limited, but is normally from 0 to 80° C., preferably room temperature.

While the reaction time varies depending on the starting materials, the reagents and the temperature used, it is normally from 5 minutes to 30 hours; and in the case where the reaction is carried out at room temperature, it is preferably from 30 minutes to 10 hours.

After the reaction, the desired compound (3) of the present reaction is obtained, for example, by, after suitably neutralizing the reaction mixture, and removing any insoluble matter, if present, by filtration, addition of water and an immiscible organic solvent such as ethyl acetate, followed by washing with water, separating the organic layer containing the desired compound, drying with anhydrous magnesium sulfate or the like, and distilling off the solvent. The thus obtained desired compound can be further purified by ordinary methods such as recrystallization, reprecipitation or chromatography, if necessary.

(Step A-2)

The present step is a step, wherein compound (4) is produced by allowing compound (2) to react with tris-(1,2,4-triazolyl)phosphite in an inert solvent (preferably a halogenated hydrocarbon such as methylene chloride), and adding water thereto to cause H-phosphonation.

The reaction temperature is not particularly limited, but is normally from −20 to 100° C., preferably from 10 to 40° C.

While the reaction time varies depending on the starting materials, the reagents and the temperature used, it is normally from 5 minutes to 30 hours; and in the case where the reaction is carried out at room temperature, it is preferably 30 minutes.

After the reaction, the desired compound (4) of the present reaction is obtained, for example, by, after suitably neutralizing the reaction mixture, and removing any insoluble matter, if present, by filtration, addition of water and an immiscible organic solvent such as ethyl acetate, followed by washing with water, separating the organic layer containing the desired compound, drying with anhydrous magnesium sulfate or the like, and distilling off the solvent. The thus obtained desired compound can be further purified by ordinary methods such as recrystallization, reprecipitation or chromatography, if necessary.

(Step A-3)

The present step is a step, wherein compound (5) is produced by allowing compound (2) to react with a bis(1,2,4-triazolyl)arylphosphate, bis(1,2,4-triazolyl)benzylphosphate, bis(1,2,4-triazolyl)-2-cyanoethylphosphate, bis(1,2,4-triazolyl)(2,2,2-trichloroethyl)phosphate or bis(1,2,4-triazolyl)(2-propenyl)phosphate in an inert solvent (preferably a halogenated hydrocarbon such as methylene chloride), and adding water thereto to make a phosphodiester.

The bis(1,2,4-triazolyl)arylphosphate to be used can be, for example, bis(1,2,4-triazolyl)phenylphosphate, bis(1,2,4-triazolyl)(2-chlorophenyl)phosphate, bis(1,2,4-triazolyl)(4-chlorophenyl)phosphate, bis(1,2,4-triazolyl)(2-nitrophenyl)phosphate or bis(1,2,4-triazolyl)(4-nitrophenyl)phosphate, and is preferably bis(1,2,4-triazolyl)(2-chlorophenyl)phosphate or bis(1,2,4-triazolyl)(4-chlorophenyl)phosphate.

The reaction temperature is not particularly limited, but is normally from −20 to 100° C., preferably from 10 to 40° C.

While the reaction time varies depending on the starting materials, the reagents and the temperature used, it is normally from 5 minutes to 30 hours; and in the case where the reaction is carried out at room temperature, it is preferably 30 minutes.

After the reaction, the desired compound (5) of the present reaction is obtained, for example, by, after suitably neutralizing the reaction mixture, and removing any insoluble matter, if present, by filtration, addition of water and an immiscible organic solvent such as ethyl acetate, followed by washing with water, separating the organic layer containing the desired compound, drying with anhydrous magnesium sulfate or the like, and distilling off the solvent. The thus obtained desired compound can be further purified by ordinary methods such as recrystallization, reprecipitation or chromatography, if necessary.

(Step B-1)

The present step is a step, wherein compound (7) is produced by allowing compound (6) to react with a protecting reagent in the presence of a basic catalyst in an inert solvent.

The solvent to be used can preferably be an aromatic hydrocarbon such as benzene, toluene or xylene; a halogenated hydrocarbon such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cyclohexanone; a nitro compound such as nitroethane or nitrobenzene; a nitrile such as acetonitrile or isobutyronitrile; an amide such as formamide, dimethylformamide (DMF), dimethylacetamide or hexamethylphosphortriamide; a sulfoxide such as dimethyl sulfoxide or sulfolane; an aliphatic tertiary amine such as trimethylamine, triethylamine or N-methylmorpholine; or an aromatic amine such as pyridine or picoline; and is more preferably a halogenated hydrocarbon (particularly methylene chloride) or an aromatic amine (particularly pyridine).

The protecting reagent to be used is not particularly limited so long as it is adapted for the following nucleic acid synthesis and can be removed under acidic or neutral conditions, and can preferably be a tri-arylmethyl halide such as trityl chloride, mono-methoxytrityl chloride or dimethoxytrityl chloride; or a triarylmethanol ether such as dimethoxytrityl-O-triflate.

In the case of using a tri-arylmethyl halide as the protecting reagent, a base is normally used. In that case, the base to be used can be a heterocyclic amine such as pyridine, dimethylaminopyridine or pyrrolidinopyridine; or an aliphatic tertiary amine such as trimethylamine or triethylamine; and is preferably pyridine, dimethylaminopyridine or pyrrolidinopyridine.

In the case of using a liquid base as the solvent, since the base itself functions as a deoxidizer, it is not necessary to add a further base.

The reaction temperature varies depending on the starting materials, the reagents and the solvent used, and is normally from 0 to 150° C., preferably from 20 to 100° C. While the reaction time varies depending on the starting materials, the solvent and the reaction temperature used, it is normally from 1 to 100 hours, preferably from 2 to 24 hours.

After the reaction, the desired compound (7) of the present reaction is obtained, for example, by concentrating the reaction mixture, adding water and an immiscible organic solvent such as ethyl acetate, followed by washing with water, separating the organic layer containing the desired compound, drying with anhydrous magnesium sulfate or the like, and distilling off the solvent.

The resulting compound can be further purified by ordinary methods, for example, recrystallization or silica gel column chromatography, if necessary.

(Step B-2)

The present step is a step, wherein compound (8) is produced by allowing compound (7) prepared in Step B-1 to react with a mono-substituted chloro(alkoxy)phosphine, di-substituted alkoxyphosphine, mono-substituted chloro(benzyloxy)phosphine or di-substituted benzyloxyphosphine, which is normally used for amidite formation, in an inert solvent.

The present step is carried out similarly to Step (A-1).

(Step B-3)

The present step is a step, wherein compound (9) is produced by allowing compound (7) prepared in Step B-1 to react with tris-(1,2,4-triazolyl)phosphite in an inert solvent (preferably a halogenated hydrocarbon such as methylene chloride), followed by adding water to carry out H-phosphonation.

The present step is carried out similarly to Step (A-2).

(Step B-4)

The present step is a step, wherein compound (8) is produced by allowing compound (7) prepared in Step B-1 to react with a bis(1,2,4-triazolyl)arylphosphate, bis(1,2,4-triazolyl)benzylphosphate, bis(1,2,4-triazolyl)-2-cyanoethylphosphate, bis(1,2,4-triazolyl) (2,2,2-trichloroethyl)phosphate, or bis(1,2,4-triazolyl) (2-propenyl)phosphate in an inert solvent (preferably a halogenated hydrocarbon such as methylene chloride), followed by adding water to make a phosphodiester.

The present step is carried out similarly to Step A-3.

(Step C-1)

The present step is a step, wherein compound (12) is produced by allowing compound (11) to react with a mono-substituted chloro(alkoxy)phosphine, di-substituted alkoxyphosphine, mono-substituted chloro(benzyloxy)phosphine, or di-substituted benzyloxyphosphine normally used for amidite formation, in an inert solvent.

Compound (11) is a compound wherein a nucleoside has been reacted with an alkyl halide such as methyl iodide or an alkenyl halide such as allyl bromide in the presence of sodium hydride, according to the method described in PCT/US94/10131, to obtain the 3′-substituted compound, and then the 5′-hydroxyl group, and amino group of the base portion, have been protected by protecting groups. For example, 3′-O-allyladenosine (catalogue No.: RP-3101) can be purchased from ChemGene Industries, and 5′-O-dimethoxytrityl-3′-O-allyl-N-benzoyladenosine can be obtained therefrom by protection using publicly known methods.

The present step is carried out similarly to Step A-1.

Amongst compounds (12), 5′-O-dimethoxytrityl-3′-O-methyl-N-benzoyladenosine-2′-O-(2-cyanoethyl N,N-diisopropylphosphoramidite) (catalogue No.: ANP-2901), for example, can be purchased from ChemGene Industries.

(Step D-1)

The present step is a step, wherein compound (14) is produced by allowing compound (13) to react with a mono-substituted chloro(alkoxy)phosphine, di-substituted alkoxyphosphine, mono-substituted chloro(benzyloxy)phosphine, or di-substituted benzyloxyphosphine normally used for amidite formation, in an inert solvent.

Compound (13) is the same compound as compound (20) described in Process F of Japanese Patent Application (Kokai) No. 2002-249497, or the compound described in Japanese Patent Application (Kokai) No. Hei 10-195098 in which Y₁ is a protecting group and Y₂ is a hydrogen atom.

The present step is carried out similarly to Step (A-1).

(Step E-1)

The present step is a step, wherein compound (16) is produced by allowing compound (15) to react with a protecting reagent in the presence of a basic catalyst in an inert solvent.

The present step is carried out similarly to Step (B-1).

(Step E-2)

The present step is a step, wherein compound (17) is produced by allowing compound (16) prepared in Step E-1 to react with a dicarboxylic anhydride in an inert solvent.

The solvent to be used is not particularly limited so long as it does not inhibit the reaction and dissolves the starting material to a certain extent, and can be, for example, an aromatic hydrocarbon such as benzene, toluene or xylene; a halogenated hydrocarbon such as methylene chloride or chloroform; an ether such as ether, tetrahydrofuran, dioxane or dimethoxyethane; an amide such as dimethylformamide, dimethylacetamide or hexamethylphosphortriamide; a sulfoxide such as dimethyl sulfoxide; a ketone such as acetone or methyl ethyl ketone; a heterocyclic amine such as pyridine; or a nitrile such as acetonitrile; and is preferably a halogenated hydrocarbon such as methylene chloride.

The deoxidizer to be used can be a pyridine such as pyridine, dimethylaminopyridine or pyrrolidinopyridine, and is preferably dimethylaminopyridine.

The dicarboxylic anhydride to be used is not limited so long as it is the anhydride of an α,ω-alkyl dicarboxylic acid having from 3 to 16 carbon atoms, and can preferably be succinic anhydride.

While the reaction temperature and the reaction time vary depending on the acid anhydride and deoxidizer used, in the case where succinic anhydride is used, and dimethylaminopyridine is used as the deoxidizer, the reaction is carried out at room temperature for 30 minutes.

After the reaction, the desired compound is collected from the reaction mixture according to ordinary methods. For example, after suitably neutralizing the reaction mixture and removing any insoluble matter, if present, by filtration, water and an immiscible organic solvent such as ethyl acetate are added, followed by washing with water, separating the organic layer containing the desired compound, drying the extract with anhydrous magnesium sulfate or the like, and distilling off the solvent to obtain the desired compound. The resulting desired compound can be further purified by ordinary methods, for example, recrystallization, reprecipitation or chromatography if necessary.

(Step E-3)

The present step is a step, wherein active ester (18) is formed by reaction of the carboxyl group of compound (17) having a free carboxyl group with an ester-forming reagent in an inert solvent, and then reaction with a phenol which may be substituted.

The solvent to be used is not particularly limited so long as it does not inhibit the reaction, and it can be an aromatic hydrocarbon such as benzene, toluene or xylene; a halogenated hydrocarbon such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cyclohexanone; a nitro compound such as nitroethane or nitrobenzene; a nitrile such as acetonitrile or isobutyronitrile; an amide such as formamide, dimethylformamide (DMF), dimethylacetamide or hexamethylphosphortriamide; or a sulfoxide such as dimethyl sulfoxide or sulfolane; and is preferably a halogenated hydrocarbon (particularly methylene chloride) or an amide (particularly dimethylformamide).

The phenol to be used is not particularly limited so long as it can be used as an active ester, and it can be 4-nitrophenol, 2,4-dinitrophenol, 2,4,5-trichlorophenol, 2,3,4,5,6-pentachlorophenol or 2,3,5,6-tetrafluorophenol, and is preferably pentachlorophenol.

The ester-forming reagent to be used can be, for example, an N-hydroxy compound such as N-hydroxysuccinimide, 1-hydroxybenzotriazole or N-hydroxy-5-norbornene-2,3-dicarboxyimide; a diimidazole compound such as 1,1′-oxalyldiimidazole or N,N′-carbonyldiimidazole; a disulfide compound such as 2,2′-dipyridyldisulfide; a succinic acid compound such as N,N′-disuccinimidylcarbonate; a phosphinic chloride compound such as N,N′-bis(2-oxo-3-oxazolidinyl)phosphinic chloride; an oxalate compound such as N,N′-disuccinimidyloxalate (DSO), N,N-diphthalimidyloxalate (DPO), N,N′-bis(norbornenylsuccinimidyl)oxalate (BNO), 1,1′-bis(benzotriazolyl)oxalate (BBTO), 1,1′-bis(6-chlorobenzotriazolyl)oxalate (BCTO) or 1,1′-bis(6-trifluoromethylbenzotriazolyl)oxalate (BTBO); or a carbodiimide such as dicyclohexylcarbodiimide (DCC); and is preferably a diimidazole compound or a carbodiimide (particularly DCC).

While the reaction temperature and the reaction time vary depending on the ester-forming reagent and the kind of the solvent used, the reaction is carried out at from 0° C. to 100° C. for from 5 to 50 hours and, particularly in the case where pentachlorophenol and DCC are used in DMF, the reaction is carried out at room temperature for 18 hours.

After the reaction, the desired compound is collected from the reaction mixture according to ordinary methods. For example, after suitably neutralizing the reaction mixture and removing any insoluble matter, if present, by filtration, water and an immiscible organic solvent such as ethyl acetate are added, followed by washing with water, separating the organic layer containing the desired compound, drying the extract with anhydrous magnesium sulfate or the like, and distilling off the solvent to obtain the desired compound. The resulting desired compound can be further purified by ordinary methods, for example, recrystallization, reprecipitation or chromatography if necessary.

(Step E-4)

The present step is a step, wherein high molecular weight derivative (20), which can be used as a carrier for oligonucleotide synthesis, is produced by allowing compound (18) having an activated carboxyl group obtained in Step E-3 to react with a high molecular weight substance (19), such as a control pore glass (CPG) bonded to an amino group, a hydroxyl group, a sulfhydryl group or the like through an alkylene group, in an inert solvent.

The high molecular weight substance (19) used in the present step is not particularly limited so long as it is used as a carrier, but it is necessary to examine the particle size of the carrier, the size of surface area by a three-dimensional network structure, the ratio of hydrophilic group positions, the chemical composition, strength against pressure, and the like.

The carrier to be used can be a polysaccharide derivative such as cellulose, dextran or agarose; a synthetic polymer such as polyacrylamide gel, polystyrene resin or polyethylene glycol; or an inorganic substance such as silica gel, porous glass or a metal oxide. Specifically, it can be a commercially available carrier such as aminopropyl-CPG, long chain aminoalkyl-CPG (these are manufactured by CPG Inc.), Cosmoseal NH₂, Cosmoseal Diol (these are manufactured by Nacalai Tesque), CPC-Silica Carrier Silane Coated, aminopropyl-CPG-550 Å, aminopropyl-CPG-1400 Å, polyethylene glycol 5000 monomethyl ether (these are manufactured by Furuka Inc.), p-alkoxybenzyl alcohol resin, aminomethyl resin, hydroxymethyl resin (these are manufactured by Kokusan Kagaku Inc.) and polyethylene glycol 14000 monomethyl ether (these are manufactured by Union Carbide Inc.), but it is not limited to these.

Further, the functional group bonded to the carrier can preferably be an amino group, a sulfhydryl group, or a hydroxyl group.

The solvent used in the present step is not particularly limited so long as it does not inhibit the reaction and dissolves the starting material to a certain extent, and it can preferably be an aromatic hydrocarbon such as benzene, toluene or xylene; a halogenated hydrocarbon such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cyclohexanone; a nitro compound such as nitroethane or nitrobenzene; a nitrile such as acetonitrile or isobutyronitrile; an amide such as formamide, dimethylformamide (DMF), dimethylacetamide or hexamethylphosphortriamide; or a sulfoxide such as dimethyl sulfoxide or sulfolane; and is preferably a halogenated hydrocarbon (particularly methylene chloride), or an amide (particularly dimethylformamide).

The reaction temperature is normally from −20 to 150° C., preferably from 0 to 50° C. The reaction time varies depending on the starting materials, the solvent, and the reaction temperature used, but it is normally from 1 to 200 hours, preferably from 24 to 100 hours. After the reaction, the desired compound is collected from the reaction mixture according to ordinary methods. For example, the desired compound is obtained by recovering the high molecular weight carrier from the reaction mixture by filtration, washing with an organic solvent such as methylene chloride, and drying under reduced pressure.

(Step F-1)

The present step is a step, wherein 2-5A analog (1) is produced on a DNA automatic synthesizer by ordinary methods using the CPG (20) prepared in Step E-4, using the compounds (3), (8), (12) and (14) prepared in Step A-1, B-2, C-1 or D-1, and a commercially available phosphoramidite reagent (21).

The 2-5A analog having the desired nucleotide sequence can be synthesized according to a method described in the literature (Nucleic Acids Research, 12, 4539 (1984)), and the manual attached to the synthesizer, by a phosphoramidite method using a DNA synthesizer, for example, model 392 of Perkin Elmer Inc.

As the compound (21), for example, 5′-O-dimethoxytrityl-3′-O-(t-butyldimethylsilyl)-N-benzoyladenosine-2′-O-(2-cyanoethyl N,N-diisopropylphosphoramidite) can be purchased from ChemGene Inc. (catalogue No.: ANP-5681).

In the present step, the amidite reagent for the compounds (3), (8), (12), (14) and (21) is activated using an acid catalyst to form a phosphorous acid tri-ester bond, and it is oxidized to a phosphoric acid tri-ester using an appropriate oxidizing agent, or it is made into a thiophosphoric tri-ester using an appropriate thioating agent.

The acidic substance used as a catalyst in the condensation reaction of the present step can be an acidic substance such as a tetrazole, and is preferably tetrazole or ethylthiotetrazole. The oxidizing agent used in the oxidation reaction of the present step is not particularly limited so long as it is normally used in oxidation reactions, and is preferably an inorganic metal oxidizing agent such as a manganese oxide, i.e., potassium permanganate or manganese dioxide; a ruthenium oxide, i.e., ruthenium tetraoxide; a selenium compound, i.e., selenium dioxide; an iron compound, i.e., iron chloride; an osmium compound, i.e., osmium tetraoxide; a silver compound, i.e., silver oxide; a mercury compound, i.e., mercury acetate; a lead oxide compound, i.e., lead oxide or lead tetraoxide; a chromic acid compound, i.e., potassium chromate, a chromic acid-sulfuric acid complex, or a chromic acid-pyridine complex; or a cerium compound, i.e., cerium ammonium nitrate (CAN); an inorganic oxidizing agent such as a halogen molecule, i.e., a chlorine molecule, a bromine molecule or an iodine molecule; a periodic acid, i.e., sodium periodate; ozone; hydrogen peroxide; a nitrous acid compound, i.e., nitrous acid; a chlorous acid compound, i.e., potassium chlorite or sodium chlorite; or a persulfuric acid compound, i.e., potassium persulfate or sodium persulfate; or an organic oxidizing agent such as a reagent used in DMSO oxidation (a complex of dimethyl sulfoxide with dicyclohexylcarbodiimide, oxalyl chloride, acetic anhydride or phosphorus pentaoxide, or a complex of pyridine-sulfur trioxide) a peroxide such as t-butyl hydroperoxide; a stable cation such as triphenylmethyl cation; a succinic acid imide such as N-bromosuccinic acid imide; a hypochlorous acid compound such as t-butyl hypochlorite; an azodicarboxylic acid compound such as azodicarboxylic acid ester; a disulfide such as dimethyl disulfide, diphenyl disulfide, or dipyridyl disulfide and triphenylphosphine; a nitrous acid ester such as methyl nitrite; a carbon tetrahalide, e.g., carbon tetrabromide; or a quinone compound, e.g., 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ); preferably iodine.

The solvent to be used is not particularly limited so long as it does not inhibit the reaction and dissolves the starting material to a certain extent, and it can preferably be an aromatic hydrocarbon such as benzene, toluene or xylene; a halogenated hydrocarbon such as methylene chloride or chloroform; an ether such as ether, tetrahydrofuran, dioxane or dimethoxyethane; an amide such as dimethylformamide, dimethylacetamide or hexamethylphosphortriamide; a sulfoxide such as dimethyl sulfoxide; an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol or isoamyl alcohol; a dilute acid such as aqueous sulfuric acid; a dilute base such as aqueous sodium hydroxide; water; a ketone such as acetone or methyl ethyl ketone; a heterocyclic amine such as pyridine; or a nitrile such as acetonitrile; preferably a heterocyclic amine (particularly pyridine), a nitrile (particularly acetonitrile), an ether (particularly tetrahydrofuran), or a halogenated hydrocarbon (particularly methylene chloride).

Further, in the case where the compound is thioated, if desired, the thioate derivative can be obtained according to a method described in the literature (Tetrahedron Letters, 32, 3005 (1991), J. Am Chem. Soc., 112, 1253 (1990)) using a reagent such as sulphur, tetraethyl thiuram disulfide (TETD, Applied Biosystems Inc., or Beaucage reagent (Millipore Inc.) for forming a thioate by reacting with a phosphite.

The reaction temperature is normally from 0 to 150° C., preferably from 10 to 60° C. The reaction time varies depending on the starting materials, the solvent and the reaction temperature used, but it is normally from 1 minute to 20 hours, preferably from 1 minute to 1 hour.

In the case where the H-phosphonic acid compound (4) or (9) obtained in Step A-2 or B-3 is condensed to form a phosphoric tri-ester bond in the present step, after it is condensed, for example, in the presence of a condensing agent such as pivaloyl chloride and a deoxidizer to form the H-phosphonic acid diester bond, the H-phosphonic acid bond can be converted to the phosphoric acid diester bond using an oxidizing agent.

The solvent used in the present step is not particularly limited so long as it does not inhibit the reaction, but anhydrous acetonitrile is preferably used. As the reagent used as the condensing agent, an acid chloride of a carboxylic acid or phosphoric acid is used, and pivaloyl chloride is preferably used.

The oxidizing agent for oxidizing the ODN having a H-phosphonic acid bond to a phosphodiester type ODN is not particularly limited so long as it is normally used for oxidation reactions, and can be a inorganic metal oxidizing agent such as a manganese oxide, e.g., potassium permanganate or manganese dioxide; a ruthenium oxide, e.g., ruthenium tetraoxide; a selenium compound, e.g., selenium dioxide; an iron compound, e.g., iron chloride; an osmium compound, e.g., osmium tetraoxide; a silver compound, e.g., silver oxide; a mercury compound, e.g., mercury acetate; a lead oxide compound, e.g., lead oxide or lead tetraoxide; a chromic acid compound, e.g., potassium chromate, a chromic acid-sulfuric acid complex or a chromic acid-pyridine complex; or a cerium compound, e.g., cerium ammonium nitrate (CAN); an inorganic oxidizing agent such as a halogen molecule, e.g., a chlorine molecule, a bromine molecule or an iodine molecule; a periodic acid, e.g., sodium periodate; ozone; hydrogen peroxide; a nitrous acid compound, e.g., nitrous acid; a chlorous acid compound e.g., potassium chlorite or sodium chlorite; or a persulfuric acid compound, e.g., potassium persulfate or sodium persulfate; or an organic oxidizing agent such as a reagent used in DMSO oxidation (a complex of dimethyl sulfoxide with dicyclohexylcarbodiimide, oxalyl chloride, acetic anhydride or phosphorous pentaoxide, or a complex of pyridine-sulfur trioxide); a peroxide such as t-butylhydroperoxide; a stable cation such as triphenylmethyl cation; a succinic acid imide such as N-bromosuccinic acid imide; a hypochlorous acid compound such as t-butyl hypochlorite; an azodicarboxylic acid compound such as methyl azodicarboxylate; a disulfide such as dimethyl disulfide, diphenyl disulfide or dipyridyl disulfide and triphenylphosphine; a nitrous acid ester such as methyl nitrite; a carbon tetrahalide, e.g., carbon tetrabromide; or a quinone compound, e.g., 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ); preferably iodine molecule.

The deoxidizer to be used can be a heterocyclic amine such as pyridine or dimethylaminopyridine; or an aliphatic amine such as trimethylamine, triethylamine or diisopropylethylamine; and is preferably an aliphatic amine (particularly diisopropylethylamine). The reaction temperature is not particularly limited but it is normally from −50 to 50° C., preferably room temperature.

The reaction time varies depending on the starting materials, the reagent and the temperature used, but it is normally from 5 minutes to 30 hours, preferably in the case where the reaction is carried out at room temperature, it is 30 minutes.

The solvent in the reaction for forming a methoxyethylamino phosphate group is not particularly limited so long as it does not inhibit the reaction, but carbon tetrachloride that is normally used as a reagent is used at a solvent amount.

The reaction temperature is not particularly limited in a range of from −50 to 100° C., but in the case where the reaction is carried out at room temperature, the reaction time is from 1 to 10 hours.

Further, in the case where the phosphodiester compound (5) or (10) obtained in Step A-3 or B-4 is condensed to form the phosphate tri-ester bond in the present step, the solvent used in the present step is not particularly limited so long as it does not inhibit the reaction, but an aromatic amine such as pyridine is preferably used.

The condensing agent used in the condensation can be dicyclocarbodiimide (DCC), mesitylenesulfonic chloride (Ms-Cl), triisopropylbenzenesulfonic chloride, mesitylenesulfonic acid triazolide (MST), mesitylenesulfonic acid-3-nitrotriazolide (MSNT), triisopropylbenzenesulfonic acid tetrazolide (TPS-Te), triisopropylbenzenesulfonic acid nitroimidazolide (TPS-NI) or triisopropylbenzenesulfonic acid pyridyltetrazolide, and is preferably MSNT, TPS-Te and TPS-NI.

The reaction temperature is not particularly limited in a range of from −10 to 100° C., but the reaction is normally carried out at room temperature.

The reaction time varies depending on the solvent used and the reaction temperature, but in the case where pyridine is used as the reaction solvent, and the reaction is carried out at room temperature, it is 30 minutes.

Cleavage from CPG in the case where the 2-5 analog is bonded to CPG and removal of the protecting groups other than the substituent portion at the 5′-end described next can be carried out by a publicly known method (J. Am. Chem. Soc., 103, 3185, (1981)).

The resulting crude 2-5A analog can be confirmed by purification using a reverse phase chromatocolumn and analyzing the purity of the purified product by HPLC.

The chain length of the thus obtained oligonucleotide analog is normally from 2 to 50, preferably from 10 to 30 nucleoside units.

(Step G-1)

The present step is to prepare 2-5A analog (1) on a DNA automatic synthesizer by ordinary methods using CPG (22), using the compounds (3), (4), (5), (8), (9), (10), (12) or (14) prepared in Step A-1, A-2, A-3, B-2, B-3, B-4, C-1 or D-1 and (21).

CPG (22) is the same as the compound (24) described in Process G of Japanese Patent Application (Kokai) No. 2002-249497, and the present step is carried out similarly to Step F-1.

(Step H-1)

The present step is a step, wherein 2-5A analog (1) is produced on a DNA automatic synthesizer by ordinary methods using CPG (23), using the compounds (3), (4), (5), (8), (9), (10), (12) or (14) prepared in Step A-1, A-2, A-3, B-2, B-3, B-4, C-1 or D-1 and (21).

CPG (23) is the same as the compound (4) described in Japanese Patent Application (Kokai) No. Hei 7-53587, and the present step is carried out similarly to Step F-1.

Further, in the 2-5A analog (1), in the case where any one of R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ is a mercapto group, after the 2-5A analog (1) is synthesized and purified by Process F, G or H, a substituent can be introduced onto the mercapto group by reacting with a compound having a halide group, in the presence of a base in an inert solvent.

The halogen can be, for example, a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom, and is preferably a chlorine atom, a bromine atom, or an iodine atom.

The compound having a halide group to be used is not particularly limited so long as it is a compound having a halide group which can be reacted with a thiophosphoric acid group, and can be, for example, an “alkyl halide which may be substituted” such as an ethyl halide, a propyl halide, a butyl halide, a 2-halo ethanol, a 3-halo propanol, or a 4-halo butanol; an “acyloxyalkyl halide” such as a 2-(stearoyloxy)ethyl halide, a 2-(myristoyloxy)ethyl halide, a 2-(decanoyloxy)ethyl halide, a 2-(benzoyloxy)ethyl halide, a 2-(pivaloyloxy)ethyl halide, a 2-(2,2-dimethyloctadecanoyloxy)ethyl halide, a 3-(stearoyloxy)propyl halide, a 3-(myristoyloxy)propyl halide, a 3-(decarioyloxy)propyl halide, a 3-(benzoyloxy)propyl halide, a 3-(pivaloyloxy)propyl halide, a 3-(2,2-dimethyloctadecanoyloxy)propyl halide, a 4-(stearoyloxy)butyl halide, a 4-(myristoyloxy)butyl halide, a 4-(decanoyloxy)butyl halide, a 4-(benzoyloxy)butyl halide, a 4-(pivaloyloxy)butyl halide, or a 4-(2,2-dimethyloctadecanoyloxy)butyl halide; an “alkylcarbamoyloxyalkyl halide” such as a 2-stearylcarbamoyloxyethyl halide; or one of the following compounds:

In the above compounds, a 2-stearoyloxyethyl halide and a 2-(2,2-dimethyloctadecanoyloxy)ethyl halide are preferred.

Of the compounds having these halide groups, compounds having an ester group (—OC(═O)— or —C(═O)O—), a carbamate group (—NHC(═O)O— or —OC(═O)NH—), an amide group (—NHC(═O)— or C(═O)NH—), a thio ester group (—SC(═O)— or —C(═O)S—), a urea group (—NHC(═O)NH—), a thiocarboxylic acid ester group (—OC(═S)— or —C(═S)O—), or a thiocarboxylic acid amide group (—NHC(═S)— or —C(═S)NH—), can be prepared in the presence of a base or a condensing agent by condensation of an acid halide compound or a carboxylic acid compound with a compound having an alcohol group; condensation of a formic, acid ester halide compound with a compound having an amino group; condensation of an acid halide compound or a carboxylic acid compound with a compound having an amino group; condensation of an acid halide compound or a carboxylic acid compound with a compound having a thiol group; condensation of compounds having two kinds of amino group with phosgene; condensation of a thiocarboxylic acid compound with a compound having an alcohol group; or condensation of a thiocarboxylic acid compound with the compound having an amino group.

The base to be used can be a heterocyclic amine such as pyridine or dimethylaminopyridine; or an aliphatic amine such as trimethylamine, triethylamine or diisopropylamine; and is preferably a heterocyclic amine (particularly pyridine).

There is no particular limitation on the solvent to be used, provided that it does not inhibit the reaction and dissolves the starting material to a certain extent, and it can be water; an amide such as dimethylformamide, dimethylacetamide or hexamethylphosphortriamide; a sulfoxide such as dimethyl sulfoxide; a heterocyclic amine such as pyridine; a nitrile such as acetonitrile; or a mixture of these solvents; and is preferably dimethylformamide.

The reaction temperature is not particularly limited in a range of from −50 to 100° C., but the reaction is normally carried out at room temperature. The reaction time varies depending on the material, the reagent used, and the temperature, but it is normally from 10 hours to 100 hours.

The reaction speed can also be appropriately increased by adding an iodide salt such as tetrabutylammonium iodide.

Instead of using CPG(23) used in method H, a 2-5A antisense oligonucleotide can be synthesized by condensing a phosphoramidite serving as a linker, such as DMT-butanol-CED phosphoramidite (ChemGene) or Spacer phosphoramidite 18 (GlenResearch), to CPG to which is bonded an oligonucleotide having the desired antisense sequence that is protected with a protecting group, followed by carrying out the procedure of the present step. For example, in the case of “CPG to which is bonded an oligonucleotide protected with a protecting group”, a modified oligonucleotide can be synthesized in which the oxygen atom at the 2′ position of the sugar portion is bridged to a carbon atom at the 4′ position with an alkylene group according to the method described in Japanese Patent Application (Kokai) No. Hei 10-304889 or Japanese Patent Application (Kokai) No. 2000-297097. In addition, a modified oligonucleotide having a 2′-O-methoxyethoxy group can be synthesized by referring to the literature (Teplove, M. et al., Nat. Struct. Biol. (1999), 6, 535; Zhang H. et al., Nature Biotech. (2000), 18, 862), and a modified oligonucleotide having a 3′-amino group can be synthesized by referring to the literature (Gryaznov, S. M. et al., Proc. Natl. Acad. Sci. USA 1995, 92, 5798; Tereshko, V. et al., J. Am. Chem. Soc. 1998, 120, 269).

The antitumor activity (cytocidal activity) of the present compounds can be investigated by adding the present compounds to cancer cells in a medium, and culturing the cells, followed by counting the number of viable cells using the MTT assay method (Tim Mosmann, J. Immunological Methods, 1983: 65, 55-63), the MTS assay method (Rotter, B. A., Thompson, B. K., Clarkin, S., Owen, T. C. Nat. Toxins 1993; 1(5): 303-7), the XTT assay method (Meshulam, T., Levitz, S. M., Christin, L., Diamond, R. D. J. Infect. Dis. 1995; 172(4): 1153-6), or Trypan blue staining.

Compounds of the invention will show anti-cancer activity against any type of malignant neoplasm and leukemia that express Rnase L, a target protein of this invention, including lung cancer, colorectal cancer, breast cancer, renal cancer, melanoma and glioma.

The antivirus activity of the present compounds can be investigated using an infected cell culture system such as HeLa cells, MDCK cells, MRC-5 cells or the like, by adding the present compounds to virus cells, such as of vaccinia virus, influenza virus or cytomegalovirus, in a medium either before or after infection, culturing for a predetermined amount of time, and then measuring the virus growth inhibition rate using the plaque assay method which measures virus infection titer (Kobayashi, N., Nagata, K. Virus Experimental Protocols, Medical View Publishing), or the ELISA method which measures the level of virus antigen (Okuno, Y., Tanaka, K., Baba, K., Maeda, A., Kunita, N., Ueda, J. Clin. Microbiol., Jun. 1, 1990; 28(6): 1308-13). The present compounds have antiviral activity to the aforesaid viruses and also to hepatitis C.

The administration forms of the 2-5A analogs of general formula (1) of the present invention can include, for example, oral administration by tablets, capsules, granules, powders or syrups, or parenteral administration by injection or suppositories. These preparations are prepared by known methods using pharmaceutically acceptable carriers such as additives such as excipients (which include, for example, organic excipients such as sugar derivatives, e.g., lactose, sucrose, glucose, mannitol and sorbitol; starch derivatives, e.g., corn starch, potato starch, α-starch and dextrin; cellulose derivatives, e.g., crystalline cellulose; gum arabic; dextran; and pullulan; and inorganic excipients such as silicate derivatives, e.g., light silicic anhydride, synthetic aluminum silicate, calcium silicate and magnesium aluminate meta-silicate; phosphates, e.g., calcium hydrogenphosphate; carbonates, e.g., calcium carbonate; and sulfates, e.g., calcium sulfate), lubricants (which can include, for example, stearic acid and its metal salts such as stearic acid, calcium stearate and magnesium stearate; talc; colloidal silica; waxes such as beeswax and spermaceti; boric acid; adipic acid; sulfates such as sodium sulfate; glycol; fumaric acid; sodium benzoate; DL-leucine; sodium salts of aliphatic acids; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride; and the above starch derivatives), binders (which can include, for example, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, Macrogol, and compounds similar to the above excipients), disintegrating agents (which can include, for example, cellulose derivatives such as low substituted hydroxypropyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose calcium and internally cross-linked carboxymethyl cellulose sodium; and chemically modified starches/celluloses such as carboxymethyl starch, carboxymethyl starch sodium and cross-linked polyvinylpyrrolidone), stabilizers (which can include paraoxybenzoates such as methyl paraben and propyl paraben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid; and sorbic acid), flavoring agents (which can include, for example, sweeteners, acidifiers, perfumes or the like normally used), diluents, and the like.

While the amount of the 2-5A analog of the present invention used varies depending on the symptoms, the age, the administration method, and the like, it is desirable to administer to the patient, such as a mammal, e.g., a human, once to several times a day, and, in the case of oral administration, 0.01 mg/kg body weight (preferably 0.1 mg/kg body weight) per time as a lower limit and 1000 mg/kg body weight (preferably 100 mg/kg body weight) as an upper limit, and, in the case of intravenous administration, 0.001 mg/kg body weight (preferably 0.01 mg/kg body weight) per time as a lower limit and 100 mg/kg body weight (preferably 10 mg/kg body weight) as an upper limit corresponding to the symptoms of the patient.

Other modes of administration include topical administration (e.g., pulmonary, intratracheal and intranasal) and other parenteral administration modes including intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial administration.

Further, the preparations may be used in combination with other antitumor agents, for example, nitrosourea type chemicals such as 5FU, AraC, ACNU or BCNU, cisplatin, daunomycin, adriamycin, mitomycin C, vincristine, and taxol.

In the following, the present invention will be explained in more detail by Examples, Reference examples and Test examples.

Example 1 Synthesis of Example 1 Compound (Exemplary Compound No. 4)

The ABI Model 392 DNA/RNA Synthesizer (Applied Biosystems) was used as the DNA synthesizer. The solvents, reagents, and phosphoramidite concentrations in each synthesis cycle were the same as in the case of general natural oligonucleotide synthesis, and the products of Applied Biosystems were used for those reagents and solvents other than the phosphoramidite and sulfurizing agent. The 5′-O-DMTr-riboadenosine analog, Bz-Adenosine-RNA-500 (Glen Research) (2.0 μmol), bound to a CPG support, was used as the starting substance. Synthesis was carried out using the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite-(ChemGene) was used as the phosphoramidite in cycles 1 and 2, while the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 3. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1 and 2, while iodine was used in cycle 3.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Sulfurization (cycles 1 and 2): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

Oxidation (cycle 3): Iodine/water/pyridine/tetrahydrofuran; 15 sec.

After synthesizing the protected 2-5A analog having the desired structure in the state in which the 5′-DMTr group has been removed, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue followed by reacting for 5 hours at 30° C. to remove the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 0-13% CH₃CN (linear gradient, 30 min.); 40° C.; 10 ml/min; 254 nm), and the fractions that eluted at 20.9, 22.7, 25.4 and 28.0 minutes corresponding to the four diastereomers were collected. The present compound eluted in the vicinity of 10.55 minutes when analyzed by ion exchange HPLC (column (Tosoh DEAE-2SW (4.6×150 mm)); solution A (20% acetonitrile), solution B (20% acetonitrile and 67 mM phosphate buffer, 2 M NaCl); solution B 5→60% (15 min., linear gradient); 60° C.; 1 ml/min). (Yield: 457 nmol as UV measured value using the calculated ε=39400 (260 nm) of the adenosine trimer)) λmax (H₂O)=258.3 nm, ESI-Mass (negative): 1080.1 [M-H]⁻.

Example 2 Synthesis of Example 2 Compound (Exemplary Compound No. 1)

Synthesis was carried out using the compound of Example 17 described in Japanese Patent Application (Kokai) No. 2002-249497 (2.0 μmol) as the 5′-O-DMTr-riboadenosine analog bound to a CPG support with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 31-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycle 1, 5′-DMT-3′-(O-methyl) adenosine(bz)2′-phosphoramidite (ChemGene) was used in cycle 2, and Chemical Phosphorylation Reagent II (Glen Research) was used in cycle 3. For the oxidation or sulfurizing agent, iodine was used in cycles 1 and 2, while xanthane hydride (Tokyo Kasei Kogyo) was used in cycle 3.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 1 and 2):

Iodine/water/pyridine/tetrahydrofuran; 15 sec.

Sulfurization (cycle 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group has been removed, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue followed by reacting for 5 hours at 30° C. to remove the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethyl amine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 30 min.); 40° C.; 10 ml/min; 254 nm), and the fraction that eluted at 16.7 minutes was collected. The present compound eluted in the vicinity of 9.46 minutes when analyzed by reverse HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH7; 0-25% CH₃CN (linear gradient, 14 min); 60° C.; 10 ml/min). (Yield: 445 nmol as UV measured value at 260 nm) λmax (H₂O)=258.2 nm, ESI-Mass (negative): 1074.15 [M-H]⁻.

Example 3 Synthesis of Example 3 Compound (Exemplary Compound No. 5)

Synthesis was carried out using Bz-Adenosine-RNA 500 (Glen Research Co.) (2.0 μmol) as the 5′-O-DMTr-riboadenosine analog bound to a CPG support with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycles 1 and 2, and the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 3. Xanthane hydride (Tokyo Kasei Kogyo) was used as the sulfurizing agent in cycles 1, 2 and 3.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 1, 2 and 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure with the 5′-DMTr group still intact, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 60% CH₃CN (isocratic); 40° C.; 10 ml/min; 254 nm), and the fractions that eluted at 9.5 and 11.8 minutes as diastereomers were collected. After the solvent was distilled off under reduced pressure, 80% aqueous acetic acid was added thereto, the mixture was left to stand for 30 minutes, and the DMTr group was removed. After the solvent was distilled off, a mixture of concentrated aqueous ammonia-ethanol (4:1) was added thereto, and the mixture was left to stand for 30 minutes. After the solvent was distilled off, the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N), followed by reacting for 5 hours at 30° C. to remove the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 30 min.); 40° C.; 10 ml/min; 254 nm), and the fractions that eluted at 16.5-19.1 minutes were collected. The present compound eluted in the vicinity of 8.8-9.8 minutes when analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH7; 0-25% CH₃CN (linear gradient, 14 min); 60° C.; 1 ml/min). (Yield: 565 nmol as UV measured value at 260 nm) λmax (H₂O)=258.2 nm, ESI-Mass (negative): 1096.1 [M-H]⁻.

Example 4 Synthesis of Example 4 Compound (Exemplary Compound No. 8)

Synthesis was carried out using Bz-Adenosine-RNA 500 (Glen Research Co.) (2.0 mol) as the 5′-O-DMTr-riboadenosine analog bound to a CPG support with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycles 1 and 2 and Chemical Phosphorylation Reagent II (Glen Research Co.) was used in cycle 3. Xanthane hydride (Tokyo Kasei Kogyo) was used as the sulfurizing agent in cycles 1, 2 and 3.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 1, 2 and 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group has been removed, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue followed by reacting for 5 hours at 30° C. to remove the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 6-25% CH₃CN (linear gradient, 30 min.); 40° C.; 10 ml/min; 254 nm), and the four fractions that eluted at 13.3, 13.7, 13.9 and 14.4 minutes corresponding to the four diastereomers were collected. The present compound eluted in the vicinity of 7.2-8.0 minutes when analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-20% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min). (Yield: 252 nmol as UV measured value at 260 nm) λmax (H₂O)=258.0 nm, ESI-Mass (negative): 1052.1 [M-H]⁻.

Example 5 Synthesis of Example 5 Compound (Exemplary Compound No. 290)

30 nmol of Example 2 compound were dissolved in 30 μl of anhydrous DMF, and 1 μl of pivaloyloxymethyl chloride (Tokyo Kasei Kogyo), approximately 1 mg of tetrabutylammonium iodide (Tokyo Kasei Kogyo), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-42% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 5.6 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-42% CH₃CN (linear gradient, 14 min); 60° C.; 1 ml/min), it eluted at 7.52 minutes. Yield: 4.8 nmol, λmax (H₂O)=258 nm, ESI-Mass (negative); 1188.2 [M-H]⁻.

Example 6 Synthesis of Example 6 Compound (Exemplary Compound No. 334)

30 nmol of Example 2 compound were dissolved in 30 μl of anhydrous DMF, and 1 μl of thioacetic acid S-(2-bromo-ethyl) ester (Bauer, L. et al. J. Org. Chem. 1965, 30, 949-951), approximately 1 mg of tetrabutylammonium iodide (Tokyo Kasei Kogyo), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 4.5 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.25 minutes. Yield: 14 nmol, λmax (H₂O)=258 nm, ESI-Mass (negative); 1176.2 [M-H]⁻.

Example 7 Synthesis of Example 7 Compound (Exemplary Compound No. 953)

Synthesis was carried out using the compound of Example 17 described in Japanese Patent Application (Kokai) No. 2002-249497 (2.0 μmol) as the 5′-O-DMTr-riboadenosine analog bound to a CPG support with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycle 1, 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used in cycle 2, and Chemical Phosphorylation Reagent II (Glen Research) was used in cycle 3. For the oxidation or sulfurizing agent, iodine was used in cycle 1, and xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 2 and 3.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycle 1): Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 2 and 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group has been removed, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue followed by reacting for 5 hours at 30° C. to remove the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 20 min.); 40° C.; 10 ml/min; 254 nm), and the fractions that eluted at 12.1 and 13.0 minutes corresponding to the two diastereomers were collected. The present compound eluted in the vicinity of 8.66 and 8.98 minutes when analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min). Yield: 768 nmol as UV measured value at 260 nm, λmax (H₂O) 258 nm, ESI-Mass (negative): 1090.2 [M-H]⁻.

Example 8 Synthesis of Example 8 Compound (Exemplary Compound No. 954)

Synthesis was carried out using the compound of Example 17 described in Japanese Patent Application (Kokai) No. 2002-249497 (2.0 μmol) as the 5′-O-DMTr-riboadenosine analog bound to a CPG support with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycles 1 and 2, and Chemical Phosphorylation Reagent II (Glen Research) was used in cycle 3. For the oxidation or sulfurizing agent, iodine was used in cycle 1, and xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 2 and 3.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycle 1): Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 2 and 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group has been removed, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue followed by reacting for 5 hours at 30° C. to remove the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 20 min.); 40° C.; 10 ml/min; 254 nm), and the fractions that eluted at 11.5 and 12.4 minutes corresponding to the two diastereomers were collected. The present compound eluted in the vicinity of 8.28 and 8.60 minutes when analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min). Yield: 718 nmol as UV measured value at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative): 1076.1 [M-H]⁻.

Example 9 Synthesis of Example 9 Compound (Exemplary Compound No. 955)

30 nmol of Example 7 compound were dissolved in 30 μl of anhydrous DMF, and 1 μl of pivaloyloxymethyl chloride (Tokyo Kasei Kogyo), approximately 1 mg of tetrabutylammonium iodide (Tokyo Kasei Kogyo), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fractions at 5.5 minutes and 5.6 minutes corresponding to two diastereomers were collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.42 and 7.56 minutes. Yield: 1.8 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1204.2 [M-H]⁻.

Example 10 Synthesis of Example 10 Compound (Exemplary Compound No. 956)

30 nmol of Example 8 compound were dissolved in 30 μl of anhydrous DMF, and 1 μl of pivaloyloxymethyl chloride (Tokyo Kasei Kogyo), approximately 1 mg of tetrabutylammonium iodide (Tokyo Kasei Kogyo), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fractions at 5.7 and 5.9 minutes corresponding to two diastereomers were collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.68 and 7.85 minutes. Yield: 11 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1191.20 [M-H]⁻.

Example 11 Synthesis of Example 11 Compound (Exemplary Compound No. 957)

30 nmol of Example 7 compound were dissolved in 30 μl of anhydrous DMF, and 1 μl of thioacetic acid S-(2-bromo-ethyl) ester (Bauer, L. et al. J. Org. Chem. 1965, 30, 949-951), approximately 1 mg of tetrabutylammonium iodide (Tokyo Kasei Kogyo), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fractions at 4.7 and 4.8 minutes corresponding to two diastereomers were collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 6.57 and 6.75 minutes. Yield: 20 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1192.1 [M-H]⁻.

Example 12 Synthesis of Example 12 Compound (Exemplary Compound No. 958)

30 nmol of Example 8 compound were dissolved in 30 μl of anhydrous DMF, and 1 μl of thioacetic acid S-(2-bromo-ethyl) ester (Bauer, L. et al. J. Org. Chem. 1965, 30, 949-951), approximately 1 mg of tetrabutylammonium iodide (Tokyo Kasei Kogyo), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fractions at 4.9 and 5.1 minutes corresponding to two diastereomers were collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-43% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 6.83 and 7.04 minutes. Yield: 6.7 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1178.1 [M-H]⁻.

Example 13 Synthesis of Example 13 Compound (Exemplary Compound No. 964)

30 nmol of Example 2 compound were dissolved in 30 μl of anhydrous DMF, and 1 μl of 2-(pivaloyloxy)ethyl bromide (Preparation process described in EP0395313), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 60° C.; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 4.3 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.48 minutes. Yield: 19.1 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258.6 nm, FAB-Mass (negative); 1202 [M-H]⁻.

Example 14 Synthesis of Example 14 compound (Exemplary Compound No. 965)

30 nmol of Example 2 compound were dissolved in 30 μl of anhydrous DMF, and 1 μl of 2-(benzoyloxy)ethyl bromide (Tokyo Kasei Kogyo), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 7.0 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.44 minutes. Yield: 19.7 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258.7 nm, FAB-Mass (negative); 1222 [M-H]⁻.

Example 15 Synthesis of Example 15 Compound (Exemplary Compound No. 967)

30 nmol of Example 2 compound were dissolved in 30 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 8.2 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 14.62 minutes. Yield: 14.9 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=260.1 nm, FAB-Mass (negative); 1384 [M-H]⁻.

Example 16 Synthesis of Example 16 Compound (Exemplary Compound No. 968)

30 nmol of Example 2 compound were dissolved in 30 μl of anhydrous DMF, and 1 mg of 2-(myristoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 6.3 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 12.57 minutes. Yield: 13.1 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=259.7 nm, FAB-Mass (negative); 1328 [M-H]⁻.

Example 17 Synthesis of Example 17 Compound (Exemplary Compound No. 969)

30 nmol of Example 2 compound were dissolved in 30 μl of anhydrous DMF, and 1 mg of 2-(decanoyloxy)ethyl bromide (Devinsky, Ferdinand et al., Collect. Czech. Chem. Commun. 49, 12, 1984, 2819-2827), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 50 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 4.3 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-80% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 10.36 minutes. Yield: 19.8 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258.2 nm, FAB-Mass (negative); 1272 [M-H]⁻.

Example 18 Synthesis of Example 18 Compound (Exemplary Compound No. 1074)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (2.0 μmol) was used as the solid phase carrier. The compound of Example 16 described in Japanese Patent Application (Kokai) No. 2002-249497 was used as the phosphoramidite in cycle 1, 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycle 2, 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used in cycle 3, and the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycle 1, and iodine was used in cycles 2, 3 and 4.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 2, 3 and 4):

Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycle 1): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure, and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue, followed by reacting for 5 hours at 30° C. to remove the DMTr group and the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 5-17% CH₃CN (linear gradient, 20 min.); 40° C.; 10 ml/min; 254 nm), and the fraction that eluted at 14.9 minutes was collected. The present compound eluted in the vicinity of 6.77 minutes when analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min). Yield: 1440 nmol as UV measured value at 260 nm, λmax (H₂O)=258.5 nm, ESI-Mass (negative): 1198.1 [M-H]⁻.

Example 19 Synthesis of Example 19 Compound (Exemplary Compound No. 1075)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (2.0 μmol) was used as the solid phase carrier. The compound of Example 16 described in Japanese Patent Application (Kokai) No. 2002-249497 was used as the phosphoramidite in cycle 1, 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycle 2, 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used in cycle 3, and Chemical Phosphorylation Reagent II (Glen Research) was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1 and 4, and iodine was used in cycles 2 and 3.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 2 and 3):

Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 1 and 4): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure, and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue, followed by reacting for 5 hours at 30° C. to remove the DMTr group and the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate. (TEAA), pH 7; 5-17% CH₃CN (linear gradient, 20 min.); 40° C.; 10 ml/min; 254 nm), and the fraction that eluted at 15.5 minutes was collected. The present compound eluted in the vicinity of 8.63 minutes when analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min). Yield: 1482 nmol as UV measured value at 260 nm, λmax (H₂O)=258.2 nm, ESI-Mass (negative): 1170.1 [M-H]⁻.

Example 20 Synthesis of Example 20 Compound (Exemplary Compound No. 1937)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 31-Phosphate CPG (Glen Research) (1.0 μmol) was used as the solid phase carrier. 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used as the phosphoramidite in cycles 1 and 3, 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycle 2, and the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. Iodine was used as the oxidizing agent.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation: Iodine/water/pyridine/tetrahydrofuran; 15 sec.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure, and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue, followed by reacting for 5 hours at 30° C. to remove the DMTr group and the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 2.5-10% CH₃CN (linear gradient, 10 min.); 60° C.; 2 ml/min), and the fraction that eluted at 4.8 minutes was collected. The present compound eluted in the vicinity of 3.16 minutes when analyzed by reverse phase HPLC (column (((Merck chromolith (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-10% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min). Yield: 95 nmol as UV measured value at 260 nm, λmax (H₂O)=256.2 nm, ESI-Mass (negative): 1171.9 [M-H]⁻.

Example 21 Synthesis of Example 21 Compound (Exemplary Compound No. 1099)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (1.0 μmol) was used as the solid phase carrier. 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used as the phosphoramidite in cycles 1 and 3, 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycle 2, and the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1 and 2, and iodine was used in cycles 3 and 4.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 3 and 4):

Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 1 and 2): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure, and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue, followed by reacting for 5 hours at 30° C. to remove the DMTr group and the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm)); 0.1 M aqueous triethyl amine acetate (TEAA), pH 7; 5-10% CH₃CN (linear gradient, 10 min.); 60° C.; 2 ml/min), and the fractions that eluted at 6.0 and 6.4 minutes were collected. The present compound eluted in the vicinity of 4.89 and 5.43 minutes when analyzed by reverse phase HPLC (column (((Merck chromolith (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-10% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min). Yield: 54 nmol as UV measured value at 260 nm, λmax (H₂O)=258.0 nm, ESI-Mass (negative): 1189 [M-H]⁻.

Example 22 Synthesis of Example 22 Compound (Exemplary Compound No. 1110)

500 mg (1.6 mmol) of 2,2-Dimethyl-octadecanoic acid (Roth, Bruce D. et al., J. Med. Chem. 1992, 35(9), 1609-17) were dissolved in anhydrous dichloromethane (10 ml), and 350 mg (1.8 mmol) of dicyclohexylcarbodiimide (DCC), and 140 μl (2 mmol) of 2-bromoethanol were added thereto, followed by stirring of the mixture at room temperature overnight. The reaction mixture was purified using a silica gel column (elution by hexane-ethyl acetate (7:1) solvent mixture) to obtain 230 mg of 2-(2,2-dimethyloctadecanoyloxy)ethyl bromide to be used below.

100 nmol of Example 19 compound were dissolved in 100 μl of anhydrous DMF, and 3 mg of 2-(2,2-dimethyloctadecanoyloxy)ethyl bromide, and 3 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 33-80% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 6.7 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 9.65 minutes. Yield: 24.5 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=259.3 nm, ESI-Mass (negative); 1537.3 [M-H]⁻.

Example 23 Synthesis of Example 23 Compound (Exemplary Compound No. 1111)

100 nmol of Example 19 compound were dissolved in 100 μl of anhydrous DMF, and 3 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 3 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 52-100% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 1.9 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 15-100% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 10.06 minutes. Yield: 39.8 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258.2 nm, ESI-Mass (negative); 1508.4 [M-H]⁻.

Example 24 Synthesis of Example 24 compound (Exemplary compound No. 1112)

100 nmol of Example 19 compound were dissolved in 100 μl of anhydrous DMF, and 3 mg of 2-(myristoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 3 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 33-100% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 4.1 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 15-100% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 8.75 minutes. Yield: 54.3 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258.0 nm, ESI-Mass (negative); 1452.4 [M-H]⁻.

Example 25 Synthesis of Example 25 Compound (Exemplary Compound No. 1113)

100 nmol of Example 19 compound were dissolved in 100 μl of anhydrous DMF, and 3 mg of 2-(decanoyloxy)ethyl bromide (Devinsky, Ferdinand et al., Collect. Czech. Chem. Commun. 49, 12, 1984, 2819-2827), and 3 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 15-62% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 6.2 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 15-100% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.29 minutes. Yield: 50.9 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258.4 nm, ESI-Mass (negative); 1396.3 [M-H]⁻.

Example 26 Synthesis of Example 26 Compound (Exemplary Compound No. 1938)

30 nmol of Example 20 compound were dissolved in 30 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 100 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 28-100% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 5.3 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column Merck chromolith (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.51 minutes. Yield: 14.9 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1483.2 [M-H]⁻.

Synthesis of Example 27 Compound (Exemplary Compound No. 1183)

30 nmol Example 21 compound were dissolved in 30 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy) ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 100 μl of water were added, and the aqueous layer was washed three times with 100 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEA), pH 7; 28-100% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 5.2 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.57 minutes. Yield: 16.8 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1498.5 [M-H]⁻.

Example 28 Synthesis of Example 28 Compound (Exemplary Compound No. 1219)

100 nmol of Example 18 compound were dissolved in 100 μl of anhydrous DMF, and 3 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 3 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 72-100% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 3.3 minutes was collected. Yield: 8.6 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=260.5 nm, ESI-Mass (negative); 1791.4 [M-H]⁻.

Example 29 Synthesis of Example 29 Compound (Exemplary Compound No. 1220)

100 nmol of Example 18 compound were dissolved in 100 μl of anhydrous DMF, and 3 mg of 2-(myristoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 3 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 52-100% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 3.7 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 15-100% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 10.96 minutes. Yield: 41.6 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=259.1 nm, ESI-Mass (negative); 1679.5 [M-H]⁻.

Example 30 Synthesis of Example 30 Compound (Exemplary Compound No. 1221)

100 nmol of Example 18 compound were dissolved in 100 μl of anhydrous DMF, and 3 mg of 2-(decanoyloxy)ethyl bromide (Devinsky, Ferdinand et al., Collect. Czech. Chem. Commun. 49, 12, 1984, 2819-2827), and 3 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 34-100% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 4.5 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 15-100% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 8.92 minutes. Yield: 46.6 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=259.3 nm, ESI-Mass (negative); 1566[M-H]⁻.

Example 31 Synthesis of Example 31 Compound (Exemplary Compound No. 1362)

Synthesis was carried out using the compound of Example 17 described in Japanese Patent Application (Kokai) No. 2002-249497 (2.0 μmol) as the 5′-O-DMTr-riboadenosine analog bound to a CPG support with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycles 1 and 2, and the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 3. For the oxidation or sulfurizing agent, iodine was used in cycles 1 and 3, and xanthane hydride (Tokyo Kasei Kogyo) was used in cycle 2.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 1 and 3):

Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycle 2): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group has been removed, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue followed by reacting for 5 hours at 30° C. to remove the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 30 min.); 40° C.; 10 ml/min; 254 nm), and the fractions that eluted at 10.9 and 12.0 minutes corresponding to the two diastereomer were collected. The present compound eluted in the vicinity of 8.09 and 8.50 minutes when analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min). (Yield: 749 nmol as UV measured value at 260 nm) λmax (H₂O)=258 nm, ESI-Mass (negative): 1104.2 [M-H]⁻.

Example 32 Synthesis of Example 32 Compound (Exemplary Compound No. 1363)

Synthesis was carried out using the compound of Example 17 described in Japanese Patent Application (Kokai) No. 2002-249497 (2.0 μmol) as the 5′-0-DMTr-riboadenosine analog bound to a CPG support with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycle 1, 51-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used in cycle 2, and the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 3. For the oxidation or sulfurizing agent, iodine was used in cycles 1 and 3, and xanthane hydride (Tokyo Kasei Kogyo) was used in cycle 2.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 1 and 3):

Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycle 2): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group has been removed, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the pH was adjusted to 2.0 by adding aqueous hydrochloric acid (2 N) to the remaining residue followed by reacting for 5 hours at 30° C. to remove the silyl group. After neutralizing with aqueous ammonia and distilling off the solvent, the product was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (GL Science Inertsil Prep-ODS (20×250 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 30 min.); 40° C.; 10 ml/min; 254 nm), and the fractions that eluted at 11.5 and 12.7 minutes corresponding to the two diastereomers were collected. The present compound eluted in the vicinity of 8.48 and 8.97 minutes when analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min). (Yield: 555 nmol as UV measured value at 260 nm) λmax (H₂O)=258 nm, ESI-Mass (negative): 1118.2 [M-H]⁻.

Example 33 Synthesis of Example 33 Compound (Exemplary Compound No. 1369)

100 nmol of Example 2 compound were dissolved in 50 μl of anhydrous DMF, and 2 μl of 2-bromoethanol (Tokyo Kasei Kogyo), and 2 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 200 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-25% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 6.4 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 12.54 minutes. Yield: 20.3 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258.1 nm, ESI-Mass (negative); 1118.2[M-H]⁻.

Example 34 Synthesis of Example 34 Compound (Exemplary Compound No. 1394)

100 nmol of Example 19 compound were dissolved in 50 μl of anhydrous DMF, and 2 μl of 2-bromoethanol (Tokyo Kasei Kogyo), and 2 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 200 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-25% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min; 254 nm), and the fraction at 6.0 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 0-15% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 11.60 minutes. Yield: 48.2 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258.0 nm, ESI-Mass (negative); 1242.2 [M-H]⁻.

Example 35 Synthesis of Example 35 Compound (Exemplary Compound No. 1645)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (0.5 μmol) was used as the solid phase carrier. The compound of Example 16 described in Japanese Patent Application (Kokai) No. 2002-249497 was used as the phosphoramidite in cycle 1, 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used in cycle 2, 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used in cycle 3, and the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1, 2 and 3, and iodine was used in cycle 4.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycle 4): Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 1, 2 and 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the remaining residue was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 10 min.); 60° C.; 2 ml/min), and the fractions that eluted at 4.8-5.2 minutes corresponding to the four diastereomers were collected.

After the solvent was evaporated under reduced pressure, 1 ml of aqueous hydrochloric acid (0.01N) was added to the remaining residue to accurately adjust the pH to 2.0, followed by reaction at 30° C. for 5 hours to remove the DMTr group and the silyl group. After neutralization with aqueous ammonia, the deprotected silanol and DMTrOH were removed by extraction with ethyl acetate to obtain the desired compound. When the present compound was analyzed by reverse phase HPLC (column (Merck chromolith (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-25% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), it eluted at 4.72 and 5.06 minutes. Yield: 70 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=258 nm, ESI-Mass (negative); 1230.1 [M-H]⁻.

Example 36 Synthesis of Example 36 Compound (Exemplary Compound No. 1646)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (0.5 μmol) was used as the solid phase carrier. The compound of Example 16 described in Japanese Patent Application (Kokai) No. 2002-249497 was used as the phosphoramidite in cycle 1, 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used in cycle 2, 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used in cycle 3, and the compound of Example 8a described in Japanese Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1 and 2, and iodine was used in cycles 3 and 4.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 3 and 4):

Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 1 and 2): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the remaining residue was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 10 min.); 60° C.; 2 ml/min), and the fractions that eluted at 4.7-5.0 minutes corresponding to the two diastereomers were collected.

After the solvent was evaporated under reduced pressure, 1 ml of aqueous hydrochloric acid (0.01N) was added to the remaining residue to accurately adjust the pH to 2.0, followed by reaction at 30° C. for 5 hours to remove the DMTr group and the silyl group. After neutralization with aqueous ammonia, the deprotected silanol and DMTrOH were removed by extraction with ethyl acetate to obtain the desired compound. When the present compound was analyzed by reverse phase HPLC (column (Merck chromolith (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-20% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), it eluted at 4.12 and 4.44 minutes. Yield: 95 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=258 nm, ESI-Mass (negative); 1214.2 [M-H]⁻.

Example 37 Synthesis of Example 37 Compound (Exemplary Compound No. 1648)

40 nmol of Example 35 compound were dissolved in 40 μl of anhydrous DMF, and 1 mg of 2-(2,2-dimethyloctadecanoyloxy)ethyl bromides described in Example 22, and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.4 minutes was collected. Yield: 12.6 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1568.3 [M-H]⁻.

Example 38 Synthesis of Example 38 Compound (Exemplary Compound No. 1649)

40 nmol of Example 36 compound were dissolved in 40 μl of anhydrous DMF, and 1 mg of 2-(2,2-dimethyloctadecanoyloxy)ethyl bromide described in Example 22, and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.4 minutes was collected. Yield: 21.8 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1552.3 [M-H]⁻.

Example 39 Synthesis of Example 39 Compound (Exemplary Compound No. 1651)

40 nmol of Example 35 compound were dissolved in 40 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.7 minutes was collected. Yield: 11.4 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1540.3 [M-H]⁻.

Example 40 Synthesis of Example 40 Compound (Exemplary Compound No. 1652)

40 nmol of Example 36 compound were dissolved in 40 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 7.0 minutes was collected. Yield: 23.1 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1524.3 [M-H]⁻.

Example 41 Synthesis of Example 41 Compound (Exemplary Compound No. 1663)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (0.5 μmol) was used as the solid phase carrier. The compound of Example 14 described in Japanese Patent No. 3420984 was used as the phosphoramidite in cycle 1, 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used in cycle 2, 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used in cycle 3, and the compound of Example 8a described in Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1, 2 and 3, and iodine was used in cycle 4.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycle 4): Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 1, 2 and 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure, and the pH was accurately adjusted to 2.0 by adding 1 ml of aqueous hydrochloric acid (0.01 N) to the remaining residue, followed by reacting for 5 hours at 30° C. to remove the DMTr group and the silyl group. After neutralizing with aqueous ammonia, the deprotected silanol and the DMTrOH were removed by extraction with ethyl acetate to obtain the desired compound. The product eluted at 3.75, 4.12, 4.53 and 4.76 minutes when analyzed by reverse phase HPLC (column (Merck chromolith (4.6×50 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 5-20% CH₃CN (linear gradient, 10 min.); 60° C.; 2 ml/min). Yield: 111 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=258 nm, ESI-Mass (negative); 1216.1 [M-H]⁻.

Example 42 Synthesis of Example 42 Compound (Exemplary Compound No. 1664)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (0.5 μmol) was used as the solid phase carrier. The compound of Example 14 described in Japanese Patent No. 3420984 was used as the phosphoramidite in cycle 1, 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used in cycle 2, 5′-DMT-3′-(O-methyl) adenosine(N-bz)2′-phosphoramidite (ChemGene) was used in cycle 3, and the compound of Example 8a described in Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1 and 2, and iodine was used in cycles 3 and 4.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycles 3 and 4):

Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 1 and 2): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the remaining residue was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 10 min.); 60° C.; 2 ml/min), and the fractions that eluted at 4.6-4.9 minutes corresponding to the two diastereomers were collected.

After the solvent was distilled off under reduced pressure, 1 ml of aqueous hydrochloric acid (0.01N) was added to the remaining residue to accurately adjust the pH to 2.0, followed by reaction at 30° C. for 5 hours to remove the DMTr group and the silyl group. After neutralization with aqueous ammonia, the deprotected silanol and DMTrOH were removed by extraction with ethyl acetate to obtain the desired compound. When the present compound was analyzed by reverse phase HPLC (column (Merck chromolith (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-20% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min), it eluted at 2.40 and 3.01 minutes. Yield: 127 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=258 nm, ESI-Mass (negative); 1200.15 [M-H]⁻.

Example 43 Synthesis of Example 43 Compound (Exemplary Compound No. 1666)

40 nmol of Example 41 compound were dissolved in 40 μl of anhydrous DMF, and 1 mg of 2-(2,2-dimethyloctadecanoyloxy)ethyl bromide described in Example 22, and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.9 minutes was collected. Yield: 9.5 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1554.3 [M-H]⁻.

Example 44 Synthesis of Example 44 Compound (Exemplary Compound No. 1667)

40 nmol of Example 42 compound were dissolved in 40 μl of anhydrous DMF, and 1 mg of 2-(2,2-dimethyloctadecanoyloxy)ethyl bromide described in Example 22, and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.9 minutes was collected. Yield: 4.6 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1538.3 [M-H]⁻.

Example 45 Synthesis of Example 45 Compound (Exemplary Compound No. 1669)

80 nmol of Example 41 compound were dissolved in 100 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of pyridine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 500 μl of water were added, and the aqueous layer was washed three times with 500 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.6 minutes was collected. Yield: 40.4 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1526.3 [M-H]⁻.

Example 46 Synthesis of Example 46 Compound (Exemplary Compound No. 1670)

80 nmol of Example 42 compound were dissolved in 100 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of pyridine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 500 μl of water were added, and the aqueous layer was washed three times with 500 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.6 minutes was collected. Yield: 41.9 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=259 nm, ESI-Mass (negative); 1510.29 [M-H]⁻.

Example 47 Synthesis of Example 47 Compound (Exemplary Compound No. 1690)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (0.5 μmol) was used as the solid phase carrier. 5′-DMT-3′-(O-methyl) Adenosine(N-bz)2′-phosphoramidite (ChemGene) was used as the phosphoramidite in cycles 1 and 3, 3′-tBDSilyl-riboAdenosine (N-bz) phosphoramidite (ChemGene) was used in cycle 2, and the compound of Example 8a described in Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1, 2 and 3, and iodine was used in cycle 4.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycle 4): Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 1, 2 and 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the remaining residue was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column ((Merck chromolith (4.6×50 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 10 min.); 60° C.; 2 ml/min), and the fractions that eluted at 4.7-5.1 minutes corresponding to the two diastereomers were collected.

After the solvent was evaporated under reduced pressure, 1 ml of aqueous hydrochloric acid (0.01N) was added to the remaining residue to accurately adjust the pH to 2.0, followed by reaction at 30° C. for 5 hours to remove the DMTr group and the silyl group. After neutralization with aqueous ammonia, the deprotected silanol and DMTrOH were removed by extraction with ethyl acetate to obtain the desired compound. When the present compound was analyzed by reverse phase HPLC (column (Merck chromolith (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-20% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min), it eluted at 3.67, 4.01, 4.15 and 4.55 minutes. Yield: 140 nmol (in terms of UV measurement at 260 nm), λmax (H₂O) 258 nm, ESI-Mass (negative); 1204.1 [M-H]⁻.

Example 48 Synthesis of Example 48 Compound (Exemplary Compound No. 1691)

40 nmol of Example 47 compound were dissolved in 40 μl of anhydrous DMF, and 1 mg of 2-(2,2-dimethyloctadecanoyloxy)ethyl bromide described in Example 22, and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 7.0 minutes was collected. Yield: 2.5 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1542.3 [M-H]⁻.

Example 49 Synthesis of Example 49 Compound (Exemplary Compound No. 1692)

40 nmol of Example 47 compound were dissolved in 40 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of triethylamine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 300 μl of water were added, and the aqueous layer was washed three times with 200 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.8 minutes was collected. Yield: 29.6 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=258 nm, ESI-Mass (negative); 1514.3 [M-H]⁻.

Example 50 Synthesis of Example 50 Compound (Exemplary Compound No. 1929) HOC₂H₄O—P(═O) (OH)—K²⁻¹—P(═O)(OH)—K¹⁻¹—P(═O)(OH)—K²⁻¹—P(═O)(OH)—L₁—P(═O)(OH)—L₁-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-p-C^(e)-p-C^(n)-p-C^(n)-p-T^(n)-p-G^(n)-p-A^(n)-p-A^(n)-p-C^(n)-p-A^(n)-p-G^(n)-p-T^(n)-p-G^(e)-p-A^(e)-p-T^(e)-p-C^(e)-hp

A 2-5A analog having the desired sequence was synthesized by coupling various phosphoramidites in order based on one condensation cycle consisting of the following steps 1) to 4) using a DNA synthesizer, a synthesis program for ordinary synthesis of 1 μmol of RNA, and 1 μmol of the compound described in Example 12b of Patent Application (Kokai) No. Hei 7-87982 as the solid phase support.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (25 eq), acetonitrile/tetrazole; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation: Iodine/water/pyridine/tetrahydrofuran; 15 sec.

As the phosphoramidites used to synthesize the antisense oligonucleotide portion, adenine (dA^(bz)) phosphoramidite, guanine (dG^(ibu)) phosphoramidite, cytosine (dC^(bz)) phosphoramidite, and thymine (T) phosphoramidite (Applied Biosystems) were used for the sequences equivalent to natural type nucleotides, while the compounds of Examples 14, 27, 22 and 9 described in Japanese Patent No. 3420984 were used for the sequences equivalent to non-natural type nucleotides (A^(e), G^(e), C^(e), T^(e)). DMT-butanol-CED phosphoramidite (ChemGene) was used for the phosphoramidite equivalent to L₁, and 5′-DMT-3′-(O-methyl)adenosine(N-bz)2′-phosphoramidite (ChemGene), 3′-tBDsilyl-riboadenosine(N-bz)phosphoramidite (ChemGene), 5′-DMT-3′-(O-methyl)adenosine(N-bz)2′-phosphoramidite (ChemGene), and the phosphoramidite of Example 8a described in Patent Application (Kokai) No. Hei 11-246592, were coupled in order.

After synthesizing the protected 2-5A analog having the desired structure in the state in which the 5′-DMTr group has been removed, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the protecting group on the nucleic acid base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure, and 1 ml of triethylamine trihydrofluoride was added to the residue followed by stirring at room temperature. After 24 hours, 200 μl of H₂O were added, followed by the addition of 10 ml of 1-butanol, allowing to stand for 1 hour at −20° C., and centrifuging to obtain a pellet-like precipitate. After gently washing this pellet with EtOH, it was dissolved in 150 μl of H₂O and then subjected to electrophoresis on 15% denatured acrylamide gel (1× TBE solution (7 M urea, 0.89 M Tris, boric acid, EDTA solution (pH 8.3, Takara Shuzo), 600 V, 60 minutes). The band that absorbed UV in the gel was cut out and eluted from the gel with 1 ml of an elution buffer (0.5 M ammonium acetate, 10 mM magnesium acetate, 1 mM EDTA (pH 8.0), 0.1% SDS). The remaining gel was filtered off, 4 ml of EtOH were added to the filtrate, which was then allowed to stand for 1 hour at −20° C. followed by centrifugation to obtain a pellet-like precipitate. This was then purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck Chromolith (4.6×50 mm)); 0.1 M aqueous triethyl amine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 8 min.); 60° C.; 2 ml/min), and the fraction that eluted at 4.02 minutes was collected. The yield was 16.0 nmol (as UV measured value at 260 nm), and λmax (H₂O)=259 nm.

Example 51 Synthesis of Example 51 Compound (Exemplary Compound No. 1930) HOC₂H₄O—P(═O)(OH)—K²⁻¹—P(═O)(OH)—K¹⁻¹—P(═O)(OH)—K²⁻¹—P(═O)(OH)—L₁—P(═O)(OH)—L₁-p-T^(e)-p-C^(e)-p-T^(e)-p-T^(e)-p-G^(e)-p-G^(n)-p-T^(n)-p-T^(n)-p-G^(n)-p-T^(n)-p-A^(n)-p-A^(n)-p-G^(n)-p-A^(n)p-G^(n)-p-A^(e)-p-G^(e)-p-A^(e)-p-G^(e)-p-A^(e)-hp

The title compound was obtained according to a similar method to Example 50. The present compound was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 3.61 minutes was collected. Yield: 15.8 nmol (in terms of UV measurement at 260 mm), λmax (H₂O)=257 nm.

Example 52 Synthesis of Example 52 Compound (Exemplary compound No. 1931) HOC₂H₄O—P(═O)(OH)—K²⁻¹—P(═O)(OH)—K¹⁻¹—P(═O)(OH)—K²⁻¹—P(═O)(OH)—L₁—P(═O)(OH)—L₁-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-p-G^(e)-p-G^(n)-p-C^(n)-p-C^(n)-p-T^(n)-p-C^(n)-p-C^(n)-p-A^(n)-p-T^(n)-p-A^(n)-p-T^(n)-p-G^(e)-p-G^(e)-p-A^(e)-p-A^(e)-p-T^(e)-hp

The title compound was obtained according to a similar method to Example 50. The present compound was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 3.66 minutes was collected. Yield: 7.8 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=259 nm.

Example 53 Synthesis of Example 53 Compound (Exemplary Compound No. 1932) HOC₂H₄O—P(═O)(OH)—K²⁻¹—P(═O)(OH)—K¹⁻¹—P(═O)(OH)—K²⁻¹—P(═O)(OH)—L₁-P(═O)(OH)—L₁-p-G^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-C^(n)-p-G^(n)-p-C^(n)-p-T^(n)-p-G^(n)-p-G^(n)-p-T^(n)-p-G^(n)-p-A^(n)-p-G^(n)-p-T^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

The title compound was obtained according to a similar method to Example 50. The present compound was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 8-12% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min), and the fraction at 8.0-10.0 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-29% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.54 minutes. Yield: 37.6 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=258.9 nm.

Example 54 Synthesis of Example 54 Compound (Exemplary Compound No. 1933) HOC₂H₄O—P(═O)(OH)—K²⁻¹—P(═O)(OH)—K¹⁻¹—P(═O)(OH)—K²⁻¹—P(═O)(OH)—L₁—P(═O)(OH)—L₁-p-G^(e)-p-A^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-A^(n)-p-A^(n)-p-A^(n)p-T^(n)-p-C^(n)-p-T^(n)-p-C^(n)-p-T^(n)-p-G^(n)-p-C^(n)-p-C^(e)-p-G^(e)-p-C^(e)-p-A^(e)-T^(e)-hp

The title compound was obtained according to a similar method to Example 50. The present compound was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 3.74 minutes was collected. Yield: 131 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=262 nm.

Example 55 Synthesis of Example 55 Compound (Exemplary Compound No. 1934) HOC₂H₄O—P(═O)(OH)—K²⁻¹—P(═O)(OH)—K¹⁻¹—P(═O)(OH)—K²⁻¹—P(═O)(OH)—L₁—P(═O)(OH)—L₁-p-A^(e)-p-T^(e)-p-G^(e)-p-G^(e)-p-C^(e)-p-A^(n)-p-C^(n)-p-C^(n)-p-T^(n)-p-C^(n)-p-T^(n)-p-T^(n)-p-G^(n)-p-T^(n)-p-G^(n)-p-G^(e)-p-A^(e)-p-C^(e)-p-C^(e)-p-A^(e)-hp

The title compound was obtained according to a similar method to Example 50. The present compound was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 3.83 minutes was collected. Yield: 5.5 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=261 nm.

Example 56 Synthesis of Example 56 Compound (Exemplary Compound No. 1935) HOC₂H₄O—P(═O)(OH)—K²⁻¹—P(═O)(OH)—K¹⁻¹—P(═O)(OH)—K²⁻¹—P(═O)(OH)—L₁—P(═O)(OH)—L₁-p-C^(e)-p-A^(e)-p-G^(e)-p-C^(e)-p-C^(e)-p-A^(n)-p-T^(n)-p-G^(n)-p-G^(n)-p-T^(n)-p-C^(n)-p-C^(n)-p-C^(n)-p-C^(n)-p-C^(n)-p-C^(e)-p-C^(e)-p-C^(e)-p-A^(e)-p-A^(e)-hp

The title compound was obtained according to a similar method to Example 50. The present compound was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 9-25% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 3.25 minutes was collected. Yield: 55 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=266 nm.

Example 57 Synthesis of Example 57 Compound (Exemplary Compound No. 1936) HOC₂H₄O—P(═O)(OH)—K²⁻¹—P(═O)(OH)—K¹⁻¹—P(═O)(OH)—K²⁻¹—P(═O)(OH)-L₂-p-G^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-T^(e)-p-C^(n)-p-G^(n)-p-C^(n)-p-T^(n)-p-G^(n)-p-G^(n)-p-T^(n)-p-G^(n)-p-A^(n)-p-G^(n)-p-T^(e)-p-T^(e)-p-T^(e)-p-C^(e)-p-A^(e)-hp

The title compound was obtained according to a similar method to Example 50. Here, Spacer phosphoramidite 18 (Glen Research Inc.) was used as the phosphoramidite corresponding to L₂. The present compound was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 8-12% CH₃CN (linear gradient, 10 min); 60° C.; 2 ml/min), and the fraction at 8.0-10.0 minutes was collected. When the present compound was analyzed by reverse phase HPLC (column (Tosoh superODS (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 5-29% CH₃CN (linear gradient, 10 min); 60° C.; 1 ml/min), it eluted at 7.52 minutes. Yield: 59.5 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=258.6 nm.

Example 58 Synthesis of Example 58 Compound (Exemplary Compound No. 1103)

Synthesis was carried out with the DNA synthesizer based on one condensation cycle consisting of the following steps 1) to 4) using a synthesis program for ordinary synthesis of 1 μmol of RNA. 3′-Phosphate CPG (Glen Research) (0.2 mol) was used as the solid phase carrier. 3′-tBDSilyl-ribo Adenosine (N-bz) phosphoramidite (ChemGene) was used as the phosphoramidite in cycles 1, 2 and 3, and the compound of Example 8a described in Patent Application (Kokai) No. Hei 11-246592 was used in cycle 4. For the oxidation or sulfurizing agent, xanthane hydride (Tokyo Kasei Kogyo) was used in cycles 1, 2 and 3, and iodine was used in cycle 4.

Condensation Cycle:

1) Detritylation: Trichloroacetic acid/dichloromethane; 85 sec.

2) Coupling: Phosphoramidite (about 25 eq)/acetonitrile, tetrazole/acetonitrile; 10 to 20 min.

3) Capping: 1-methylimidazole/tetrahydrofuran, acetic anhydride/pyridine/tetrahydrofuran; 15 sec.

4) Oxidation (cycle 4): Iodine/water/pyridine/tetrahydrofuran; 15 sec.

sulfurization (cycles 1, 2 and 3): Xanthane hydride (0.02 M)/acetonitrile-pyridine (9:1 mixed solvent); 15 min.

After synthesizing the 2-5A analog having the desired structure in the state in which the 5′-DMTr group is retained, together with cleaving the oligomer from the support, the cyanoethyl group serving as the protecting group on the phosphorus atom and the benzoyl group on the adenine base were removed by treating with a mixture of concentrated aqueous ammonia and ethanol (3:1). The solvent was then distilled off under reduced pressure and the remaining residue was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column ((Merck chromolith (4.6×50 mm)); 0.1 M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min.); 60° C.; 2 ml/min), and the fractions that eluted at 6.0-6.7 minutes corresponding to the four diastereomers were collected.

After the solvent was evaporated under reduced pressure, 1 ml of aqueous hydrochloric acid (0.01N) was added to the remaining residue to accurately adjust the pH to 2.0, followed by reaction at 30° C. for 5 hours to remove the DMTr group and the silyl group. After neutralization with aqueous ammonia, the deprotected silanol and DMTrOH were removed by extraction with ethyl acetate. When the remaining aqueous solution was analyzed by reverse phase HPLC (column (((Merck chromolith (4.6×50 mm)); 0.1M aqueous triethylamine acetate (TEAA), pH7; 0-20% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), the fractions that eluted at 4.6 and 5.4 minutes were collected to obtain the desired compound. Yield: 38 nmol (in terms of UV measurement at 260 nm), λmax (H₂O)=259 nm

Example 59 Synthesis of Example 59 Compound (Exemplary Compound No. 1195)

40 nmol of Example 58 compound were dissolved in 100 μl of anhydrous DMF, and 1 mg of 2-(stearoyloxy)ethyl bromide (Ackerman et al., J. Am. Chem. Soc., 78, 1956, 6025), and 1 μl of pyridine were added thereto, followed by reacting the mixture at room temperature overnight. After completion of the reaction, 500 μl of water were added, and the aqueous layer was washed three times with 500 μl of AcOEt. After the aqueous layer was evaporated, it was purified by reverse phase HPLC (Shimadzu Seisakusho LC-VP; column (Merck chromolith (4.6×50 mm); 0.1M aqueous triethylamine acetate (TEAA), pH 7; 24-100% CH₃CN (linear gradient, 8 min); 60° C.; 2 ml/min), and the fraction at 6.8 minutes was collected. Yield: 8.9 nmol in terms of UV measurement at 260 nm, λmax (H₂O)=259 nm.

Test Example 1 Measurement of Cytotoxic Activity of 2-5A Analogs (MTT Assay)

Human lung cancer cell line A549 cells were plated at a density of 800 cells/200 μl in a 96-well plate using RPMI1640 (Gibco BRL) (containing 10% Fetal Bovine Serum (Hyclone)) for the medium followed by culturing overnight in 5% CO₂ at 37° C. Each 2-5A analog was added to each well so that the final concentration became 10 μM, followed by culturing for 72 hours (3 days). After culturing for 72 hours (3 days), MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was added in 50 μl aliquots to each well at a MTT/RPMI1640 concentration of 5 mg/ml, followed by additionally culturing for 4 hours. After 4 hours, the medium was removed and 150 μl of dimethyl sulfoxide were added to each well. After shaking for 5 minutes, UV absorbance at 540 nm was measured to determine the relative ratio of the number of viable cells of the compound dose group to the number of viable cells of an untreated cell group at 72 hours after addition of the test compound.

The cytotoxic activity during addition of the subject compounds (10 μM) with respect to A549 cells is shown in the graph. In this graph, the natural type 2-5A indicates a 3 mer, 2′,5′-oligoadenylate with a 5′-monophosphate group having the structure shown below (Imai, J. and Torrence, P. F., J. Org. Chem., 1985, 50(9), 1418-1426).

As is clear from FIG. 1, during addition to the medium at a concentration of 10 μM, in contrast to natural type 2-5A not demonstrating any cytotoxic effects against human lung cancer cell line A549 cells, the subject compounds demonstrated superior cytotoxic activity.

Test Example 2 Measurement of Cytotoxic Activity of 2-5A Analogs (MTT Assay)

Human lung cancer cell line A549 cells were plated at a density of 800 cells/200 μl in a 96-well plate using RPMI1640 (Gibco BRL) (containing 10% Fetal Bovine Serum (Hyclone)) for the medium followed by culturing overnight in 5% CO₂ at 37° C. Each 2-5A analog was added to each well so that the final concentration became 0.001-10 μM, followed by culturing for 72 hours (3 days) (n=3 or 4). After culturing for 72 hours (3 days), MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was added in 50 μl aliquots to each well at a MTT/RPMI1640 concentration of 5 mg/ml, followed by additionally culturing for 4 hours. After 4 hours, the medium was removed and 150 μl of dimethyl sulfoxide were added to each well. After shaking for 5 minutes, UV absorbance at 540 nm, was measured to determine the relative ratio of the number of viable cells of the compound dose group to the number of viable cells of an untreated cell group followed by calculation of the IC₅₀ concentration that inhibits cell growth by 50%.

The table shows the 50% growth inhibitory concentrations of the subject compounds with respect to A549 cells.

TABLE 50% Growth inhibitory concentrations of the subject compounds with respect to A549 cells Experiment Experiment Experiment Experiment 1 2 3 4 Example 2 1.53 0.91 Example 4 0.48 0.61 0.38 Example 5 0.40 0.32 Example 8 2.23 Example 9 1.39 Example 13 2.54 Example 14 2.34 Example 15 0.061 0.073 Example 16 0.09 Example 17 0.35 Example 19 13 Example 22 0.33 Example 23 0.13 0.091 Example 24 0.30 Example 25 0.91 Example 26 0.15 Example 27 0.36 Example 28 0.13 Example 29 0.14 Example 30 0.43 Example 33 2.15 Example 34 6.60

As is clear from the above table, in contrast to natural type 2-5A not demonstrating any cytotoxic effects against human lung cancer cell line A549 cells even at 10 μM, the subject compounds demonstrated superior cytocidal activity.

The compounds of the present invention have stability and excellent activity (particularly antitumor activity), and are useful as pharmaceutical drugs (particularly antitumor agents). The compounds of the present invention can be administered to a mammal, such as a human, to treat a tumor or a viral disease. 

1. A 2′,5′-oligoadenylate analog represented by the formula (1):

wherein m represents an integer of 0; n represents an integer of 0 or 1; R¹ represents an alkoxy group having from 1 to 6 carbon atoms substituted by a hydroxyl group, an unprotected mercapto group, an alkylthio group having from 1 to 4 carbon atoms substituted by a hydroxyl group, or a group of a formula X₁—X₂—X₃—S—; R², R³, R⁴, R⁵ and R⁶ independently represent an unprotected hydroxyl group, an unprotected mercapto group, an alkylthio group having from 1 to 4 carbon atoms substituted by a hydroxyl group, or a group of formula X₁—X₂—X₃—S—; R⁷ represents an oxygen atom a sulfur atom, —NH—, a —O(CH₂CH₂O)q- group, wherein g represents an integer of 2 to 6, or an oxyalkyleneoxy group having from 1 to 6 carbon atoms; R⁸ represents a hydrogen atom, or a 5′-phosphorylated oligonucleotide analog which has one hydroxyl group removed from the 5′-phosphoric acid group; E¹ represents K²; E² represents K¹; E³ represents K² or K³ and E⁴ represents K¹, K² or K³, wherein K¹, K² and K³ represent, respectively,

wherein B represents an adeninyl group, A represents an alkylene group having from 1 to 4 carbon atoms, D represents an unsubstituted alkyl group having from 1 to 6 carbon atoms, or an unsubstituted alkenyl group having from 2 to 6 carbon atoms; X₁ represents an unsubstituted alkyl group having from 1 to 24 carbon atoms, or a phenyl group; X₂ represents a —C(═O)O—, —OC(═O)— or a —C(═O)S— group; and X₃ represents an unsubstituted alkylene group having from 1 to 6 carbon atoms, or a pharmacologically acceptable salt thereof.
 2. The 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof according to claim 1, wherein R¹ is an alkoxy group having from 1 to 4 carbon atoms substituted by a hydroxyl group, an unprotected mercapto group, or an alkylthio group having from 1 to 4 carbon atoms substituted by a hydroxyl group, or a group of the formula X₁—X₂—X₃—S—; X₁ is an unsubstituted alkyl group having from 10 to 24 carbon atoms; and X₃ is an unsubstituted alkylene group having from 1 to 4 carbon atoms.
 3. The 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof according to claim 1 or claim 2, wherein R⁷ represents an oxygen atom, a —O(CH₂CH₂O)q- group, wherein q represents an integer of 2 to 6, or an oxyalkyleneoxy group having from 1 to 6 carbon atoms.
 4. The 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof according to claim 1, wherein D is a methyl group or a 2-propenyl group.
 5. The 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof according to claim 1, wherein E³ is K³, and A is a methylene, ethylene, or propylene group.
 6. The 2′,5′-oligoadenylate analog according to claim 1, which is

or pharmacologically acceptable salt thereof.
 7. The 2′,5′-oligoadenylate analog according to claim 1, which is

or pharmacologically acceptable salt thereof.
 8. The 2′,5′-oligoadenylate analog or pharmacologically acceptable salt thereof according to claim 1, wherein R¹ is an alkoxy group having from 1 to 4 carbon atoms substituted by a hydroxyl group, an unprotected mercapto group, an alkylthio group having from 1 to 4 carbon atoms substituted by a hydroxyl group, or a group of formula: X₁—X₂—X₃—S—; X₂ is a —C(—O)O— or —C(═O)S— group; X₃ is an unsubstituted alkylene group having from 1 to 4 carbon atoms; R⁷ represents an oxygen atom, a —O(CH₂CH₂O)q- group, wherein q represents an integer of 2 to 6, or an oxyalkyleneoxy group having from 1 to 6 carbon atoms; D is a methyl group or a 2-propenyl group; E³ is K³; and A is a methylene, ethylene group or propylene group; and B is 6-aminopurin-9-yl or 6-amino-8-bromopurin-9-yl.
 9. The 2′,5′-oligoadenylate analog according to claim 1, which is

or a pharmacologically acceptable salt thereof.
 10. The 2′,5′-oligoadenylate analog according to claim 1, which is

or a pharmacologically acceptable salt thereof.
 11. The 2′,5′-oligoadenylate analog according to claim 1, which is

or a pharmacologically acceptable salt thereof.
 12. The 2′,5′-oligoadenylate analog according to claim 1, which is

or a pharmacologically acceptable salt thereof.
 13. The 2′,5′-oligoadenylate analog according to claim 1, which is

or a pharmacologically acceptable salt thereof.
 14. The 2′,5′-oligoadenylate analog according to claim 1, which is

or a pharmacologically acceptable salt thereof.
 15. A pharmaceutical composition comprising a pharmaceutically effective amount of the 2′,5′-oligoadenylate analog according to claim 1 or a pharmacologically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.
 16. A method for treating lung cancer comprising administering to a human in need thereof a pharmaceutically effective amount of the 2′,5′-oligoadenylate analog according to claim 1 or a pharmaceutically acceptable salt thereof.
 17. The method according to claim 16, wherein the 2′,5′-oligoadenylate analog is selected from the group consisting of

or a pharmacologically acceptable salt thereof.
 18. The method according to claim 16, wherein the 2′,5′-oligoadenylate analog is selected from the group consisting of

or a pharmacologically acceptable salt thereof. 